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Review Article | Open Access

Long noncoding RNA XIST: Mechanisms for X chromosome inactivation, roles in sex-biased diseases, and therapeutic opportunities

Jianjian Li1, Zhe Ming1, Liuyi Yang1, Tingxuan Wang, Gaowen Liu, Qing Ma( )
Shenzhen Key Laboratory of Synthetic Genomics, Guangdong Provincial Key Laboratory of Synthetic Genomics, CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, PR China

1 These authors contributed equally to this work.

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Abstract

Sexual dimorphism has been reported in various human diseases including autoimmune diseases, neurological diseases, pulmonary arterial hypertension, and some types of cancers, although the underlying mechanisms remain poorly understood. The long noncoding RNA (lncRNA) X-inactive specific transcript (XIST) is involved in X chromosome inactivation (XCI) in female placental mammals, a process that ensures the balanced expression dosage of X-linked genes between sexes. XIST is abnormally expressed in many sex-biased diseases. In addition, escape from XIST-mediated XCI and skewed XCI also contribute to sex-biased diseases. Therefore, its expression or modification can be regarded as a biomarker for the diagnosis and prognosis of many sex-biased diseases. Genetic manipulation of XIST expression can inhibit the progression of some of these diseases in animal models, and therefore XIST has been proposed as a potential therapeutic target. In this manuscript, we summarize the current knowledge about the mechanisms for XIST-mediated XCI and the roles of XIST in sex-biased diseases, and discuss potential therapeutic strategies targeting XIST.

Keywords

Long noncoding RNAEpigenetic regulationSex-biased diseasesX chromosome inactivationXIST

References

1

Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;10(3): 155-159.
Crossref Google Scholar
2

Gil N, Ulitsky I. Regulation of gene expression by cis-acting long non-coding RNAs. Nat Rev Genet. 2020;21(2): 102-117.
Crossref Google Scholar
3

Quinodoz SA, Jachowicz JW, Bhat P, et al. RNA promotes the formation of spatial compartments in the nucleus. Cell. 2021;184(23): 5775-5790. e30.
Crossref Google Scholar
4

Razin SV, Gavrilov AA. Non-coding RNAs in chromatin folding and nuclear organization. Cell Mol Life Sci. 2021;78(14): 5489-5504.
Crossref Google Scholar
5

Tachiwana H, Yamamoto T, Saitoh N. Gene regulation by non-coding RNAs in the 3D genome architecture. Curr Opin Genet Dev. 2020;61: 69-74.
Crossref Google Scholar
6

Wang T, Li J, Yang L, Wu M, Ma Q. The role of long non-coding RNAs in human imprinting disorders: prospective therapeutic targets. Front Cell Dev Biol. 2021;9: 730014.
Crossref Google Scholar
7

Fatica A, Bozzoni I. Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet. 2014;15(1): 7-21.
Crossref Google Scholar
8

Bhan A, Soleimani M, Mandal SS. Long noncoding RNA and cancer: a new paradigm. Cancer Res. 2017;77(15): 3965-3981.
Crossref Google Scholar
9

Batista PJ, Chang HY. Long noncoding RNAs: cellular address codes in development and disease. Cell. 2013;152(6): 1298-1307.
Crossref Google Scholar
10

Penny GD, Kay GF, Sheardown SA, Rastan S, Brockdorff N. Requirement for Xist in X chromosome inactivation. Nature. 1996;379(6561): 131-137.
Crossref Google Scholar
11

Okamoto I, Nakamura T, Sasaki K, et al. The X chromosome dosage compensation program during the development of cynomolgus monkeys. Science. 2021;374(6570): eabd8887.
Crossref Google Scholar
12

Yu B, Qi Y, Li R, Shi Q, Satpathy AT, Chang HY. B cell-specific XIST complex enforces X-inactivation and restrains atypical B cells. Cell. 2021;184(7): 1790-1803. e17.
Crossref Google Scholar
13

Deng X, Berletch JB, Nguyen DK, Disteche CM. X chromosome regulation: diverse patterns in development, tissues and disease. Nat Rev Genet. 2014;15(6): 367-378.
Crossref Google Scholar
14

Schulz EG, Heard E. Role and control of X chromosome dosage in mammalian development. Curr Opin Genet Dev. 2013;23(2): 109-115.
Crossref Google Scholar
15

Patrat C, Ouimette JF, Rougeulle C. X chromosome inactivation in human development. Development. 2020;147(1): dev183095.
Crossref Google Scholar
16

Okamoto I, Patrat C, Thépot D, et al. Eutherian mammals use diverse strategies to initiate X-chromosome inactivation during development. Nature. 2011;472(7343): 370-374.
Crossref Google Scholar
17

Sahakyan A, Yang Y, Plath K. The role of Xist in X-chromosome dosage compensation. Trends Cell Biol. 2018;28(12): 999-1013.
Crossref Google Scholar
18

Sidorenko J, Kassam I, Kemper KE, et al. The effect of X-linked dosage compensation on complex trait variation. Nat Commun. 2019;10(1): 3009.
Crossref Google Scholar
19

Maduro C, de Hoon B, Gribnau J. Fitting the puzzle pieces: the bigger picture of XCI. Trends Biochem Sci. 2016;41(2): 138-147.
Crossref Google Scholar
20

Brown CJ, Hendrich BD, Rupert JL, et al. The human XIST gene: analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus. Cell. 1992;71(3): 527-542.
Crossref Google Scholar
21

Brown CJ, Ballabio A, Rupert JL, et al. A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature. 1991;349(6304): 38-44.
Crossref Google Scholar
22

Brockdorff N, Ashworth A, Kay GF, et al. Conservation of position and exclusive expression of mouse Xist from the inactive X chromosome. Nature. 1991;351(6324): 329-331.
Crossref Google Scholar
23

Markaki Y, Chong JG, Wang Y, et al. Xist nucleates local protein gradients to propagate silencing across the X chromosome. Cell. 2021;184(25): 6174-6192. e32.
Crossref Google Scholar
24

Żylicz JJ, Bousard A, Žumer K, et al. The implication of early chromatin changes in X chromosome inactivation. Cell. 2019;176(1–2): 182-197. e23.
Crossref Google Scholar
25

Xu N, Tsai CL, Lee JT. Transient homologous chromosome pairing marks the onset of X inactivation. Science. 2006;311(5764): 1149-1152.
Crossref Google Scholar
26

Monkhorst K, Jonkers I, Rentmeester E, Grosveld F, Gribnau J. X inactivation counting and choice is a stochastic process: evidence for involvement of an X-linked activator. Cell. 2008;132(3): 410-421.
Crossref Google Scholar
27

Jégu T, Aeby E, Lee JT. The X chromosome in space. Nat Rev Genet. 2017;18(6): 377-389.
Crossref Google Scholar
28

Furlan G, Gutierrez Hernandez N, Huret C, et al. The ftx noncoding locus controls X chromosome inactivation independently of its RNA products. Mol Cell. 2018;70(3): 462-472. e8.
Crossref Google Scholar
29

Tian D, Sun S, Lee JT. The long noncoding RNA, Jpx, is a molecular switch for X chromosome inactivation. Cell. 2010;143(3): 390-403.
Crossref Google Scholar
30

Sun S, del Rosario BC, Szanto A, Ogawa Y, Jeon Y, Lee JT. Jpx RNA activates xist by evicting CTCF. Cell. 2013;153(7): 1537-1551.
Crossref Google Scholar
31

Jonkers I, Barakat TS, Achame EM, et al. RNF12 is an X-Encoded dose-dependent activator of X chromosome inactivation. Cell. 2009;139(5): 999-1011.
Crossref Google Scholar
32

Lee JT, Davidow LS, Warshawsky D. Tsix, a gene antisense to Xist at the X-inactivation centre. Nat Genet. 1999;21(4): 400-404.
Crossref Google Scholar
33

Lee JT. Regulation of X-chromosome counting by Tsix and Xite sequences. Science. 2005;309(5735): 768-771.
Crossref Google Scholar
34

Bell AC, West AG, Felsenfeld G. The protein CTCF is required for the enhancer blocking activity of vertebrate insulators. Cell. 1999;98(3): 387-396.
Crossref Google Scholar
35

Navarro P, Page DR, Avner P, Rougeulle C. Tsix-mediated epigenetic switch of a CTCF-flanked region of the Xist promoter determines the Xist transcription program. Genes Dev. 2006;20(20): 2787-2792.
Crossref Google Scholar
36

Gontan C, Achame EM, Demmers J, et al. RNF12 initiates X-chromosome inactivation by targeting REX1 for degradation. Nature. 2012;485(7398): 386-390.
Crossref Google Scholar
37

Navarro P, Oldfield A, Legoupi J, et al. Molecular coupling of Tsix regulation and pluripotency. Nature. 2010;468(7322): 457-460.
Crossref Google Scholar
38

Makhlouf M, Ouimette JF, Oldfield A, Navarro P, Neuillet D, Rougeulle C. A prominent and conserved role for YY1 in Xist transcriptional activation. Nat Commun. 2014;5: 4878.
Crossref Google Scholar
39

Robert-Finestra T, Tan BF, Mira-Bontenbal H, et al. SPEN is required for Xist upregulation during initiation of X chromosome inactivation. Nat Commun. 2021;12(1): 7000.
Crossref Google Scholar
40

Fukuda A, Hazelbaker DZ, Motosugi N, et al. De novo DNA methyltransferases DNMT3A and DNMT3B are essential for XIST silencing for erosion of dosage compensation in pluripotent stem cells. Stem Cell Reports. 2021;16(9): 2138-2148.
Crossref Google Scholar
41

Chu C, Zhang QC, da Rocha ST, et al. Systematic discovery of Xist RNA binding proteins. Cell. 2015;161(2): 404-416.
Crossref Google Scholar
42

Grant M, Zuccotti M, Monk M. Methylation of CpG sites of two X-linked genes coincides with X-inactivation in the female mouse embryo but not in the germ line. Nat Genet. 1992;2(2): 161-166.
Crossref Google Scholar
43

Jeppesen P, Turner BM. The inactive X chromosome in female mammals is distinguished by a lack of histone H4 acetylation, a cytogenetic marker for gene expression. Cell. 1993;74(2): 281-289.
Crossref Google Scholar
44

Chaumeil J, Okamoto I, Guggiari M, Heard E. Integrated kinetics of X chromosome inactivation in differentiating embryonic stem cells. Cytogenet Genome Res. 2002;99(1–4): 75-84.
Crossref Google Scholar
45

Heard E, Rougeulle C, Arnaud D, Avner P, Allis CD, Spector DL. Methylation of histone H3 at Lys-9 is an early mark on the X chromosome during X inactivation. Cell. 2001;107(6): 727-738.
Crossref Google Scholar
46

Keniry A, Gearing LJ, Jansz N, et al. Setdb1-mediated H3K9 methylation is enriched on the inactive X and plays a role in its epigenetic silencing. Epigenetics Chromatin. 2016;9: 16.
Crossref Google Scholar
47

Pandya-Jones A, Markaki Y, Serizay J, et al. A protein assembly mediates Xist localization and gene silencing. Nature. 2020;587(7832): 145-151.
Crossref Google Scholar
48

Ridings-Figueroa R, Stewart ER, Nesterova TB, et al. The nuclear matrix protein CIZ1 facilitates localization of Xist RNA to the inactive X-chromosome territory. Genes Dev. 2017;31(9): 876-888.
Crossref Google Scholar
49

Sunwoo H, Colognori D, Froberg JE, Jeon Y, Lee JT. Repeat E anchors Xist RNA to the inactive X chromosomal compartment through CDKN1A-interacting protein (CIZ1). Proc Natl Acad Sci U S A. 2017;114(40): 10654-10659.
Crossref Google Scholar
50

Yue M, Ogawa A, Yamada N, Charles Richard JL, Barski A, Ogawa Y. Xist RNA repeat E is essential for ASH2L recruitment to the inactive X and regulates histone modifications and escape gene expression. PLoS Genet. 2017;13(7): e1006890.
Crossref Google Scholar
51

Monfort A, di Minin G, Postlmayr A, et al. Identification of spen as a crucial factor for xist function through forward genetic screening in haploid embryonic stem cells. Cell Rep. 2015;12(4): 554-561.
Crossref Google Scholar
52

Dossin F, Pinheiro I, Żylicz JJ, et al. SPEN integrates transcriptional and epigenetic control of X-inactivation. Nature. 2020;578(7795): 455-460.
Crossref Google Scholar
53

McHugh CA, Chen CK, Chow A, et al. The Xist lncRNA interacts directly with SHARP to silence transcription through HDAC3. Nature. 2015;521(7551): 232-236.
Crossref Google Scholar
54

Schoeftner S, Sengupta AK, Kubicek S, et al. Recruitment of PRC1 function at the initiation of X inactivation independent of PRC2 and silencing. EMBO J. 2006;25(13): 3110-3122.
Crossref Google Scholar
55

Almeida M, Pintacuda G, Masui O, et al. PCGF3/5-PRC1 initiates Polycomb recruitment in X chromosome inactivation. Science. 2017;356(6342): 1081-1084.
Crossref Google Scholar
56

Bousard A, Raposo AC, Żylicz JJ, et al. The role of Xist-mediated Polycomb recruitment in the initiation of X-chromosome inactivation. EMBO Rep. 2019;20(10): e48019.
Crossref Google Scholar
57

Pintacuda G, Wei G, Roustan C, et al. hnRNPK recruits PCGF3/5-PRC1 to the Xist RNA B-repeat to establish polycomb-mediated chromosomal silencing. Mol Cell. 2017;68(5): 955-969. e10.
Crossref Google Scholar
58

Lee JT, Bartolomei MS. X-inactivation, imprinting, and long noncoding RNAs in health and disease. Cell. 2013;152(6): 1308-1323.
Crossref Google Scholar
59

Dixon-McDougall T, Brown CJ. Independent domains for recruitment of PRC1 and PRC2 by human XIST. PLoS Genet. 2021;17(3): e1009123.
Crossref Google Scholar
60

Patil DP, Chen CK, Pickering BF, et al. m(6)A RNA methylation promotes XIST-mediated transcriptional repression. Nature. 2016;537(7620): 369-373.
Crossref Google Scholar
61

Coker H, Wei G, Moindrot B, Mohammed S, Nesterova T, Brockdorff N. The role of the Xist 5' m6A region and RBM15 in X chromosome inactivation. Wellcome Open Res. 2020;5: 31.
Crossref Google Scholar
62

Engreitz JM, Pandya-Jones A, McDonel P, et al. The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome. Science. 2013;341(6147): 1237973.
Crossref Google Scholar
63

Jeon Y, Lee JT. YY1 tethers Xist RNA to the inactive X nucleation center. Cell. 2011;146(1): 119-133.
Crossref Google Scholar
64

Chen CK, Blanco M, Jackson C, et al. Xist recruits the X chromosome to the nuclear Lamina to enable chromosome-wide silencing. Science. 2016;354(6311): 468-472.
Crossref Google Scholar
65

Colognori D, Sunwoo H, Kriz AJ, Wang CY, Lee JT. Xist deletional analysis reveals an interdependency between xist RNA and polycomb complexes for spreading along the inactive X. Mol Cell. 2019;74(1): 101-117. e10.
Crossref Google Scholar
66

Wutz A, Jaenisch R. A shift from reversible to irreversible X inactivation is triggered during ES cell differentiation. Mol Cell. 2000;5(4): 695-705.
Crossref Google Scholar
67

Chan KM, Zhang H, Malureanu L, van Deursen J, Zhang Z. Diverse factors are involved in maintaining X chromosome inactivation. Proc Natl Acad Sci U S A. 2011;108(40): 16699-16704.
Crossref Google Scholar
68

Schultz DC, Ayyanathan K, Negorev D, Maul GG, . SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins. Genes Dev. 2002;16(8): 919-932.
Crossref Google Scholar
69

Lopes-Ramos CM, Quackenbush J, DeMeo DL. Genome-wide sex and gender differences in cancer. Front Oncol. 2020;10: 597788.
Crossref Google Scholar
70

Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin. 2021;71(1): 7-33.
Crossref Google Scholar
71

Libert C, Dejager L, Pinheiro I. The X chromosome in immune functions: when a chromosome makes the difference. Nat Rev Immunol. 2010;10(8): 594-604.
Crossref Google Scholar
72

Park R, Chidharla A, Mehta K, Sun W, Wulff-Burchfield E, Kasi A. Sex-bias in COVID-19-associated illness severity and mortality in cancer patients: a systematic review and meta-analysis. EClinicalMedicine. 2020;26: 100519.
Crossref Google Scholar
73

Brodin P. Immune determinants of COVID-19 disease presentation and severity. Nat Med. 2021;27(1): 28-33.
Crossref Google Scholar
74

Wenham C, Smith J, Morgan R. Gender and COVID-19 Working Group. COVID-19: the gendered impacts of the outbreak. Lancet. 2020;395(10227): 846-848.
Crossref Google Scholar
75

Li CH, Prokopec SD, Sun RX, et al. Sex differences in oncogenic mutational processes. Nat Commun. 2020;11(1): 4330.
Crossref Google Scholar
76

Zhu Y, Shao X, Wang X, Liu L, Liang H. Sex disparities in cancer. Cancer Lett. 2019;466: 35-38.
Crossref Google Scholar
77

Galasso V, Pons V, Profeta P, Becher M, Brouard S, Foucault M. Gender differences in COVID-19 attitudes and behavior: panel evidence from eight countries. Proc Natl Acad Sci U S A. 2020;117(44): 27285-27291.
Crossref Google Scholar
78

Vlassoff C. Gender differences in determinants and consequences of health and illness. J Health Popul Nutr. 2007;25(1): 47-61.
Google Scholar
79

Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol. 2016;16(10): 626-638.
Crossref Google Scholar
80

Youness A, Miquel CH, Guéry JC. Escape from X chromosome inactivation and the female predominance in autoimmune diseases. Int J Mol Sci. 2021;22(3): 1114.
Crossref Google Scholar
81

Fish EN. The X-files in immunity: sex-based differences predispose immune responses. Nat Rev Immunol. 2008;8(9): 737-744.
Crossref Google Scholar
82

Pinheiro I, Dejager L, Libert C. X-chromosome-located microRNAs in immunity: might they explain male/female differences? The X chromosome-genomic context may affect X-located miRNAs and downstream signaling, thereby contributing to the enhanced immune response of females. Bioessays. 2011;33(11): 791-802.
Crossref Google Scholar
83

Berletch JB, Ma W, Yang F, et al. Escape from X inactivation varies in mouse tissues. PLoS Genet. 2015;11(3): e1005079.
Crossref Google Scholar
84

Carrel L, Willard HF. X-inactivation profile reveals extensive variability in X-linked gene expression in females. Nature. 2005;434(7031): 400-404.
Crossref Google Scholar
85

Tukiainen T, Villani AC, Yen A, et al. Landscape of X chromosome inactivation across human tissues. Nature. 2017;550(7675): 244-248.
Crossref Google Scholar
86

Balaton BP, Cotton AM, Brown CJ. Derivation of consensus inactivation status for X-linked genes from genome-wide studies. Biol Sex Differ. 2015;6: 35.
Crossref Google Scholar
87

Pyfrom S, Paneru B, Knox JJ, et al. The dynamic epigenetic regulation of the inactive X chromosome in healthy human B cells is dysregulated in lupus patients. Proc Natl Acad Sci U S A. 2021;118(24):e2024624118.
Crossref Google Scholar
88

Syrett CM, Paneru B, Sandoval-Heglund D, et al. Altered X-chromosome inactivation in T cells may promote sex-biased autoimmune diseases. JCI Insight. 2019;4(7): e126751.
Crossref Google Scholar
89

Syrett CM, Sindhava V, Sierra I, Dubin AH, Atchison M, Anguera MC. Diversity of epigenetic features of the inactive X-chromosome in NK cells, dendritic cells, and macrophages. Front Immunol. 2018;9: 3087.
Crossref Google Scholar
90

Wang J, Syrett CM, Kramer MC, Basu A, Atchison ML, Anguera MC. Unusual maintenance of X chromosome inactivation predisposes female lymphocytes for increased expression from the inactive X. Proc Natl Acad Sci U S A. 2016;113(14): E2029-E2038.
Crossref Google Scholar
91

Syrett CM, Sindhava V, Hodawadekar S, et al. Loss of Xist RNA from the inactive X during B cell development is restored in a dynamic YY1-dependent two-step process in activated B cells. PLoS Genet. 2017;13(10): e1007050.
Crossref Google Scholar
92

Cancro MP. Age-associated B cells. Annu Rev Immunol. 2020;38: 315-340.
Crossref Google Scholar
93

Karnell JL, Kumar V, Wang J, Wang S, Voynova E, Ettinger R. Role of CD11c + T-bet + B cells in human health and disease. Cell Immunol. 2017;321: 40-45.
Crossref Google Scholar
94

Celhar T, Magalhães R, Fairhurst AM. TLR7 and TLR9 in SLE: when sensing self Goes wrong. Immunol Res. 2012;53(1–3): 58-77.
Crossref Google Scholar
95

Woodruff MC, Ramonell RP, Nguyen DC, et al. Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19. Nat Immunol. 2020;21(12): 1506-1516.
Crossref Google Scholar
96

Dunford A, Weinstock DM, Savova V, et al. Tumor-suppressor genes that escape from X-inactivation contribute to cancer sex bias. Nat Genet. 2017;49(1): 10-16.
Crossref Google Scholar
97

Pinto EM, Chen X, Easton J, et al. Genomic landscape of paediatric adrenocortical tumours. Nat Commun. 2015;6: 6302.
Crossref Google Scholar
98

Jiang L, Gu ZH, Yan ZX, et al. Exome sequencing identifies somatic mutations of DDX3X in natural killer/T-cell lymphoma. Nat Genet. 2015;47(9): 1061-1066.
Crossref Google Scholar
99

Dalgliesh GL, Furge K, Greenman C, et al. Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes. Nature. 2010;463(7279): 360-363.
Crossref Google Scholar
100

Ntziachristos P, Tsirigos A, Welstead GG, et al. Contrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukaemia. Nature. 2014;514(7523): 513-517.
Crossref Google Scholar
101

Shi B, Li W, Song Y, et al. UTX condensation underlies its tumour-suppressive activity. Nature. 2021;597(7878): 726-731.
Crossref Google Scholar
102

van Haaften G, Dalgliesh GL, Davies H, et al. Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer. Nat Genet. 2009;41(5): 521-523.
Crossref Google Scholar
103

Van der Meulen J, Sanghvi V, Mavrakis K, et al. The H3K27me3 demethylase UTX is a gender-specific tumor suppressor in T-cell acute lymphoblastic leukemia. Blood. 2015;125(1): 13-21.
Crossref Google Scholar
104

Kaneko S, Li X. X chromosome protects against bladder cancer in females via a KDM6A-dependent epigenetic mechanism. Sci Adv. 2018;4(6): eaar5598.
Crossref Google Scholar
105

Hu Y, Deng C, Zhang H, Zhang J, Peng B, Hu C. Long non-coding RNA XIST promotes cell growth and metastasis through regulating miR-139-5p mediated Wnt/β-catenin signaling pathway in bladder cancer. Oncotarget. 2017;8(55): 94554-94568.
Crossref Google Scholar
106

Fang J, Sun CC, Gong C. Long noncoding RNA XIST acts as an oncogene in non-small cell lung cancer by epigenetically repressing KLF2 expression. Biochem Biophys Res Commun. 2016;478(2): 811-817.
Crossref Google Scholar
107

Liu JL, Zhang WQ, Zhao M, Huang MY. Upregulation of long noncoding RNA XIST is associated with poor prognosis in human cancers. J Cell Physiol. 2019;234(5): 6594-6600.
Crossref Google Scholar
108

Liu A, Liu L, Lu H. LncRNA XIST facilitates proliferation and epithelial-mesenchymal transition of colorectal cancer cells through targeting miR-486-5p and promoting neuropilin-2. J Cell Physiol. 2019;234(8): 13747-13761.
Crossref Google Scholar
109

Sun N, Zhang G, Liu Y. Long non-coding RNA XIST sponges miR-34a to promotes colon cancer progression via Wnt/β-catenin signaling pathway. Gene. 2018;665: 141-148.
Crossref Google Scholar
110

Song H, He P, Shao T, Li Y, Li J, Zhang Y. Long non-coding RNA XIST functions as an oncogene in human colorectal cancer by targeting miR-132-3p. J BUON. 2017;22(3): 696-703.
Google Scholar
111

Sun W, Zu Y, Fu X, Deng Y. Knockdown of lncRNA-XIST enhances the chemosensitivity of NSCLC cells via suppression of autophagy. Oncol Rep. 2017;38(6): 3347-3354.
Crossref Google Scholar
112

Wang H, Shen Q, Zhang X, et al. The long non-coding RNA XIST controls non-small cell lung cancer proliferation and invasion by modulating miR-186-5p. Cell Physiol Biochem. 2017;41(6): 2221-2229.
Crossref Google Scholar
113

Zhang YL, Li XB, Hou YX, Fang NZ, You JC, Zhou QH. The lncRNA XIST exhibits oncogenic properties via regulation of miR-449a and Bcl-2 in human non-small cell lung cancer. Acta Pharmacol Sin. 2017;38(3): 371-381.
Crossref Google Scholar
114

Zhou X, Xu X, Gao C, Cui Y. XIST promote the proliferation and migration of non-small cell lung cancer cells via sponging miR-16 and regulating CDK8 expression. Am J Transl Res. 2019;11(9): 6196-6206.
Google Scholar
115

Zhang XT, Pan SX, Wang AH, Kong QY, Jiang KT, Yu ZB. Long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) plays a critical role in predicting clinical prognosis and progression of colorectal cancer. Med Sci Monit. 2019;25: 6429-6435.
Crossref Google Scholar
116

Hu B, Shi G, Li Q, Li W, Zhou H. Long noncoding RNA XIST participates in bladder cancer by downregulating p53 via binding to TET1. J Cell Biochem. 2019;120(4): 6330-6338.
Crossref Google Scholar
117

Liu X, Cui L, Hua D. Long noncoding RNA XIST regulates miR-137-EZH2 axis to promote tumor metastasis in colorectal cancer. Oncol Res. 2018;27(1): 99-106.
Crossref Google Scholar
118

Xu R, Zhu X, Chen F, et al. LncRNA XIST/miR-200c regulates the stemness properties and tumourigenicity of human bladder cancer stem cell-like cells. Cancer Cell Int. 2018;18: 41.
Crossref Google Scholar
119

Zhou K, Yang J, Li X, Chen W. Long non-coding RNA XIST promotes cell proliferation and migration through targeting miR-133a in bladder cancer. Exp Ther Med. 2019;18(5): 3475-3483.
Crossref Google Scholar
120

Li C, Wan L, Liu Z, et al. Long non-coding RNA XIST promotes TGF-β-induced epithelial-mesenchymal transition by regulating miR-367/141-ZEB2 axis in non-small-cell lung cancer. Cancer Lett. 2018;418: 185-195.
Crossref Google Scholar
121

Qiu HB, Yang K, Yu HY, Liu M. Downregulation of long non-coding RNA XIST inhibits cell proliferation, migration, invasion and EMT by regulating miR-212-3p/CBLL1 axis in non-small cell lung cancer cells. Eur Rev Med Pharmacol Sci. 2019;23(19): 8391-8402.
Google Scholar
122

Jiang Q, Xing W, Cheng J, Yu Y. Knockdown of lncRNA XIST suppresses cell tumorigenicity in human non-small cell lung cancer by regulating miR-142-5p/PAX6 axis. Onco Targets Ther. 2020;13: 4919-4929.
Crossref Google Scholar
123

Rong H, Chen B, Wei X, et al. Long non-coding RNA XIST expedites lung adenocarcinoma progression through upregulating MDM2 expression via binding to miR-363-3p. Thorac Cancer. 2020;11(3): 659-671.
Crossref Google Scholar
124

Wang X, Zhang G, Cheng Z, et al. Knockdown of LncRNA-XIST suppresses proliferation and TGF-β1-induced EMT in NSCLC through the Notch-1 pathway by regulation of miR-137. Genet Test Mol Biomarkers. 2018;22(6): 333-342.
Crossref Google Scholar
125

Xiong Y, Wang L, Li Y, Chen M, He W, Qi L. The long non-coding RNA XIST interacted with miR-124 to modulate bladder cancer growth, invasion and migration by targeting androgen receptor (AR). Cell Physiol Biochem. 2017;43(1): 405-418.
Crossref Google Scholar
126

Lombard AP, Mudryj M. The emerging role of the androgen receptor in bladder cancer. Endocr Relat Cancer. 2015;22(5): R265-277.
Crossref Google Scholar
127

Laor E, Schiffman ZJ, Braunstein JD, et al. Androgen receptors in bladder tumors. Urology. 1985;25(2): 161-163.
Crossref Google Scholar
128

Miyamoto H, Yang Z, Chen YT, et al. Promotion of bladder cancer development and progression by androgen receptor signals. J Natl Cancer Inst. 2007;99(7): 558-568.
Crossref Google Scholar
129

Garg M, Maurya N. WNT/β-catenin signaling in urothelial carcinoma of bladder. World J Nephrol. 2019;8(5): 83-94.
Crossref Google Scholar
130

Overdevest JB, Knubel KH, Duex JE, et al. CD24 expression is important in male urothelial tumorigenesis and metastasis in mice and is androgen regulated. Proc Natl Acad Sci U S A. 2012;109(51): E3588–E3596.
Crossref Google Scholar
131

Groenendijk FH, de Jong J, Fransen van de Putte EE, et al. ERBB2 mutations characterize a subgroup of muscle-invasive bladder cancers with excellent response to neoadjuvant chemotherapy. Eur Urol. 2016;69(3): 384-388.
Crossref Google Scholar
132

Inoue S, Ide H, Mizushima T, Jiang G, Kawahara T, Miyamoto H. ELK1 promotes urothelial tumorigenesis in the presence of an activated androgen receptor. Am J Cancer Res. 2018;8(11): 2325-2336.
Google Scholar
133

Zhao W, Li S, Tang D, et al. Androgen receptor expression in male breast cancer predicts inferior outcome and poor response to tamoxifen treatment. Eur J Endocrinol. 2014;171(4): 527-533.
Crossref Google Scholar
134

Chen DL, Chen LZ, Lu YX, et al. Long noncoding RNA XIST expedites metastasis and modulates epithelial-mesenchymal transition in colorectal cancer. Cell Death Dis. 2017;8(8): e3011.
Crossref Google Scholar
135

Zhang R, Wang Z, Yu Q, et al. Atractylenolide II reverses the influence of lncRNA XIST/miR-30a-5p/ROR1 axis on chemo-resistance of colorectal cancer cells. J Cell Mol Med. 2019;23(5): 3151-3165.
Crossref Google Scholar
136

Yang LG, Cao MZ, Zhang J, Li XY, Sun QL. LncRNA XIST modulates HIF-1A/AXL signaling pathway by inhibiting miR-93-5p in colorectal cancer. Mol Genet Genomic Med. 2020;8(4): e1112.
Crossref Google Scholar
137

Li W, He Y, Cheng Z. Long noncoding RNA XIST knockdown suppresses the growth of colorectal cancer cells via regulating microRNA-338-3p/PAX5 axis. Eur J Cancer Prev. 2021;30(2): 132-142.
Crossref Google Scholar
138

Zeng ZL, Lu JH, Wang Y, et al. The lncRNA XIST/miR-125b-2-3p axis modulates cell proliferation and chemotherapeutic sensitivity via targeting Wee1 in colorectal cancer. Cancer Med. 2021;10(7): 2423-2441.
Crossref Google Scholar
139

Yip KW, Reed JC. Bcl-2 family proteins and cancer. Oncogene. 2008;27(50): 6398-6406.
Crossref Google Scholar
140

Firestein R, Bass AJ, Kim SY, et al. CDK8 is a colorectal cancer oncogene that regulates beta-catenin activity. Nature. 2008;455(7212): 547-551.
Crossref Google Scholar
141

Marei HE, Althani A, Afifi N, et al. p53 signaling in cancer progression and therapy. Cancer Cell Int. 2021;21(1): 703.
Crossref Google Scholar
142

Yang X, Zhang S, He C, et al. METTL14 suppresses proliferation and metastasis of colorectal cancer by down-regulating oncogenic long non-coding RNA XIST. Mol Cancer. 2020;19(1): 46.
Crossref Google Scholar
143

Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3): 209-249.
Crossref Google Scholar
144

Zheng R, Lin S, Guan L, et al. Long non-coding RNA XIST inhibited breast cancer cell growth, migration, and invasion via miR-155/CDX1 axis. Biochem Biophys Res Commun. 2018;498(4): 1002-1008.
Crossref Google Scholar
145

Huang YS, Chang CC, Lee SS, Jou YS, Shih HM. Xist reduction in breast cancer upregulates AKT phosphorylation via HDAC3-mediated repression of PHLPP1 expression. Oncotarget. 2016;7(28): 43256-43266.
Crossref Google Scholar
146

Liu B, Luo C, Lin H, Ji X, Zhang E, Li X. Long noncoding RNA XIST acts as a ceRNA of miR-362-5p to suppress breast cancer progression. Cancer Biother Radiopharm. 2021;36(6): 456-466.
Crossref Google Scholar
147

Xing F, Liu Y, Wu SY, et al. Loss of XIST in breast cancer activates MSN-c-Met and reprograms microglia via exosomal miRNA to promote brain metastasis. Cancer Res. 2018;78(15): 4316-4330.
Crossref Google Scholar
148

Kim JH, Sharma A, Dhar SS, et al. UTX and MLL4 coordinately regulate transcriptional programs for cell proliferation and invasiveness in breast cancer cells. Cancer Res. 2014;74(6): 1705-1717.
Crossref Google Scholar
149

Xu Y, Wang J, Wang J. Long noncoding RNA XIST promotes proliferation and invasion by targeting miR-141 in papillary thyroid carcinoma. Onco Targets Ther. 2018;11: 5035-5043.
Crossref Google Scholar
150

Liu H, Deng H, Zhao Y, Li C, Liang Y. LncRNA XIST/miR-34a axis modulates the cell proliferation and tumor growth of thyroid cancer through MET-PI3K-AKT signaling. J Exp Clin Cancer Res. 2018;37(1): 279.
Crossref Google Scholar
151

Du YL, Liang Y, Cao Y, Liu L, Li J, Shi GQ. LncRNA XIST promotes migration and invasion of papillary thyroid cancer cell by modulating miR-101-3p/CLDN1 axis. Biochem Genet. 2021;59(2): 437-452.
Crossref Google Scholar
152

Hu Y, Mei XQ, Tang D. Long non-coding RNA XIST is down-regulated and correlated to better prognosis in ovarian cancer. Math Biosci Eng. 2020;17(3): 2070-2081.
Crossref Google Scholar
153

Huang R, Zhu L, Zhang Y. XIST lost induces ovarian cancer stem cells to acquire taxol resistance via a KMT2C-dependent way. Cancer Cell Int. 2020;20: 436.
Crossref Google Scholar
154

Wang C, Qi S, Xie C, Li C, Wang P, Liu D. Upregulation of long non-coding RNA XIST has anticancer effects on epithelial ovarian cancer cells through inverse downregulation of hsa-miR-214-3p. J Gynecol Oncol. 2018;29(6): e99.
Crossref Google Scholar
155

Guo T, Yuan D, Zhang W, et al. Upregulation of long noncoding RNA XIST has anticancer effects on ovarian cancer through sponging miR-106a. Hum Cell. 2021;34(2): 579-587.
Crossref Google Scholar
156

Huang KC, Rao PH, Lau CC, et al. Relationship of XIST expression and responses of ovarian cancer to chemotherapy. Mol Cancer Ther. 2002;1(10): 769-776.
Google Scholar
157

Meng Q, Wang N, Duan G. Long non-coding RNA XIST regulates ovarian cancer progression via modulating miR-335/BCL2L2 axis. World J Surg Oncol. 2021;19(1): 165.
Crossref Google Scholar
158

Jiang R, Zhang H, Zhou J, et al. Inhibition of long non-coding RNA XIST upregulates microRNA-149-3p to repress ovarian cancer cell progression. Cell Death Dis. 2021;12(2): 145.
Crossref Google Scholar
159

Zhu H, Zheng T, Yu J, Zhou L, Wang L. LncRNA XIST accelerates cervical cancer progression via upregulating Fus through competitively binding with miR-200a. Biomed Pharmacother. 2018;105: 789-797.
Crossref Google Scholar
160

Chen X, Xiong D, Ye L, et al. Up-regulated lncRNA XIST contributes to progression of cervical cancer via regulating miR-140-5p and ORC1. Cancer Cell Int. 2019;19: 45.
Crossref Google Scholar
161

Liu X, Xie S, Zhang J, Kang Y. Long noncoding RNA XIST contributes to cervical cancer development through targeting miR-889-3p/SIX1 axis. Cancer Biother Radiopharm. 2020;35(9): 640-649.
Crossref Google Scholar
162

Gong X, Bacchelli E, Blasi F, et al. Analysis of X chromosome inactivation in autism spectrum disorders. Am J Med Genet B Neuropsychiatr Genet. 2008;147B(6): 830-835.
Crossref Google Scholar
163

Guo L, Zhong MB, Zhang L, Zhang B, Cai D. Sex differences in Alzheimer's disease: insights from the multiomics landscape. Biol Psychiatr. 2022;91(1): 61-71.
Crossref Google Scholar
164

Brand BA, Blesson AE, Smith-Hicks CL. The impact of X-chromosome inactivation on phenotypic expression of X-linked neurodevelopmental disorders. Brain Sci. 2021;11(7): 904.
Crossref Google Scholar
165

Plenge RM, Hendrich BD, Schwartz C, et al. A promoter mutation in the XIST gene in two unrelated families with skewed X-chromosome inactivation. Nat Genet. 1997;17(3): 353-356.
Crossref Google Scholar
166

Talebizadeh Z, Bittel DC, Veatch OJ, Kibiryeva N, Butler MG. Brief report: non-random X chromosome inactivation in females with autism. J Autism Dev Disord. 2005;35(5): 675-681.
Crossref Google Scholar
167

Sripathy S, Leko V, Adrianse RL, et al. Screen for reactivation of MeCP2 on the inactive X chromosome identifies the BMP/TGF-β superfamily as a regulator of XIST expression. Proc Natl Acad Sci U S A. 2017;114(7): 1619-1624.
Crossref Google Scholar
168

Good KV, Vincent JB, Ausió J. MeCP2: the genetic driver of rett syndrome epigenetics. Front Genet. 2021;12: 620859.
Crossref Google Scholar
169

Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet. 1999;23(2): 185-188.
Crossref Google Scholar
170

Xiol C, Vidal S, Pascual-Alonso A, et al. X chromosome inactivation does not necessarily determine the severity of the phenotype in Rett syndrome patients. Sci Rep. 2019;9(1): 11983.
Crossref Google Scholar
171

Wang J, Song W. Regulation of LRRK2 promoter activity and gene expression by Sp1. Mol Brain. 2016;9: 33.
Crossref Google Scholar
172

Lee BD, Dawson VL, Dawson TM. Leucine-rich repeat kinase 2 (LRRK2) as a potential therapeutic target in Parkinson's disease. Trends Pharmacol Sci. 2012;33(7): 365-373.
Crossref Google Scholar
173

Cao J, Zhuang Y, Zhang J, et al. Leucine-rich repeat kinase 2 aggravates secondary brain injury induced by intracerebral hemorrhage in rats by regulating the P38 MAPK/Drosha pathway. Neurobiol Dis. 2018;119: 53-64.
Crossref Google Scholar
174

Di Maio R, Hoffman EK, Rocha EM, et al. LRRK2 activation in idiopathic Parkinson's disease. Sci Transl Med. 2018;10(451): eaar5429.
Crossref Google Scholar
175

Zhou Q, Zhang MM, Liu M, Tan ZG, Qin QL, Jiang YG. LncRNA XIST sponges miR-199a-3p to modulate the Sp1/LRRK2 signal pathway to accelerate Parkinson's disease progression. Aging (Albany NY). 2021;13(3): 4115-4137.
Crossref Google Scholar
176

Du Y, Gao G, Li J, et al. Silencing of long noncoding RNA XIST attenuated Alzheimer's disease-related BACE1 alteration through miR-124. Cell Biol Int. 2020;44(2): 630-636.
Crossref Google Scholar
177

Yan XW, Liu HJ, Hong YX, Meng T, Du J, Chang C. lncRNA XIST induces Aβ accumulation and neuroinflammation by the epigenetic repression of NEP in Alzheimer's disease. J Neurogenet. 2022;36(1): 11-20.
Crossref Google Scholar
178

Qin S, Predescu DN, Patel M, Drazkowski P, Ganesh B, Predescu SA. Sex differences in the proliferation of pulmonary artery endothelial cells: implications for plexiform arteriopathy. J Cell Sci. 2020;133(9): jcs237776.
Crossref Google Scholar
179

Batton KA, Austin CO, Bruno KA, Burger CD, Shapiro BP, Fairweather D. Sex differences in pulmonary arterial hypertension: role of infection and autoimmunity in the pathogenesis of disease. Biol Sex Differ. 2018;9(1): 15.
Crossref Google Scholar
180

Qin S, Predescu D, Carman B, et al. Up-regulation of the long noncoding RNA X-inactive-specific transcript and the sex bias in pulmonary arterial hypertension. Am J Pathol. 2021;191(6): 1135-1150.
Crossref Google Scholar
181

Patel M, Predescu D, Tandon R, et al. A novel p38 mitogen-activated protein kinase/Elk-1 transcription factor-dependent molecular mechanism underlying abnormal endothelial cell proliferation in plexogenic pulmonary arterial hypertension. J Biol Chem. 2013;288(36): 25701-25716.
Crossref Google Scholar
182

Atkins GB, Jain MK. Role of Krüppel-like transcription factors in endothelial biology. Circ Res. 2007;100(12): 1686-1695.
Crossref Google Scholar
183

Shapiro S, Traiger GL, Turner M, McGoon MD, Wason P, Barst RJ. Sex differences in the diagnosis, treatment, and outcome of patients with pulmonary arterial hypertension enrolled in the registry to evaluate early and long-term pulmonary arterial hypertension disease management. Chest. 2012;141(2): 363-373.
Crossref Google Scholar
184

Mair KM, Johansen AK, Wright AF, Wallace E, MacLean MR. Pulmonary arterial hypertension: basis of sex differences in incidence and treatment response. Br J Pharmacol. 2014;171(3): 567-579.
Crossref Google Scholar
185

Xu DQ, Luo Y, Liu Y, et al. Beta-estradiol attenuates hypoxic pulmonary hypertension by stabilizing the expression of p27kip1 in rats. Respir Res. 2010;11(1): 182.
Crossref Google Scholar
186

Yuan P, Wu WH, Gao L, et al. Oestradiol ameliorates monocrotaline pulmonary hypertension via NO, prostacyclin and endothelin-1 pathways. Eur Respir J. 2013;41(5): 1116-1125.
Crossref Google Scholar
187

Ye Y, Wang H, Chu JH, et al. Atractylenolide II induces G1 cell-cycle arrest and apoptosis in B16 melanoma cells. J Ethnopharmacol. 2011;136(1): 279-282.
Crossref Google Scholar
188

Huang MY, Jiang XM, Xu YL, et al. Platycodin D triggers the extracellular release of programed death Ligand-1 in lung cancer cells. Food Chem Toxicol. 2019;131: 110537.
Crossref Google Scholar
189

Peng Y, Fan JY, Xiong J, Lou Y, Zhu Y. miR-34a enhances the susceptibility of gastric cancer to platycodin D by targeting survivin. Pathobiology. 2019;86(5–6): 296-305.
Crossref Google Scholar
190

Lu JJ, Lu DZ, Chen YF, et al. Proteomic analysis of hepatocellular carcinoma HepG2 cells treated with platycodin D. Chin J Nat Med. 2015;13(9): 673-679.
Crossref Google Scholar
191

Chen D, Chen T, Guo Y, Wang C, Dong L, Lu C. Platycodin D (PD) regulates LncRNA-XIST/miR-335 axis to slow down bladder cancer progression in vitro and in vivo. Exp Cell Res. 2020;396(1): 112281.
Crossref Google Scholar
192

Chen Y, Li Z, Chen X, Zhang S. Long non-coding RNAs: from disease code to drug role. Acta Pharm Sin B. 2021;11(2): 340-354.
Crossref Google Scholar
193

Setten RL, Rossi JJ, Han SP. The Current state and future directions of RNAi-based therapeutics. Nat Rev Drug Discov. 2019;18(6): 421-446.
Crossref Google Scholar
194

Rinaldi C, Wood MJA. Antisense oligonucleotides: the next frontier for treatment of neurological disorders. Nat Rev Neurol. 2018;14(1): 9-21.
Crossref Google Scholar
195

Gardiner KJ. Molecular basis of pharmacotherapies for cognition in Down syndrome. Trends Pharmacol Sci. 2010;31(2): 66-73.
Crossref Google Scholar
196

Jiang J, Jing Y, Cost GJ, et al. Translating dosage compensation to trisomy 21. Nature. 2013;500(7462): 296-300.
Crossref Google Scholar
197

Chiang JC, Jiang J, Newburger PE, Lawrence JB. Trisomy silencing by XIST normalizes Down syndrome cell pathogenesis demonstrated for hematopoietic defects in vitro. Nat Commun. 2018;9(1): 5180.
Crossref Google Scholar
198

Spiering AE, de Vries TJ. Why females do better: the X chromosomal TLR7 gene-dose effect in COVID-19. Front Immunol. 2021;12: 756262.
Crossref Google Scholar
199

Kopp F, Mendell JT. Functional classification and experimental dissection of long noncoding RNAs. Cell. 2018;172(3): 393-407.
Crossref Google Scholar
Genes & Diseases
Volume 9 Issue 6,
November 2022
Pages 1478-1492
DOI: 10.1016/j.gendis.2022.04.007
Cite this article:
Li J, Ming Z, Yang L, et al. Long noncoding RNA XIST: Mechanisms for X chromosome inactivation, roles in sex-biased diseases, and therapeutic opportunities. Genes & Diseases, 2022, 9(6): 1478-1492. https://doi.org/10.1016/j.gendis.2022.04.007

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Received: 21 February 2022
Revised: 16 April 2022
Accepted: 18 April 2022
Published: 29 April 2022
© 2022, Chongqing Medical University.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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