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Research Article | Open Access

SRSFs mediate the function of AR in the ovarian granulosa cells of patients with PCOS

Jing Luoa,Hong YebLijuan HaobYixuan SunaRuohan LiaYanxi LiaZhu Yanga( )
Gynecology and Obstetrics of the Second Affiliated Hospital of Chongqing Medical University, Chongqing, PR China
Gynecologic Endocrinology of Chongqing Health Center for Women and Children, Chongqing, PR China

Peer review under responsibility of Chongqing Medical University.

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Abstract

Ovarian hyperandrogenism is one of the characteristics of polycystic ovary syndrome (PCOS) and androgen receptor (AR) in ovarian granulosa cells (GCs) functions as an important element to the accumulation of androgens. This study verified the existence of alternative splicing variant of AR (AR-SVs) in the GCs of PCOS patients and found that the function of AR decreased significantly in the presence of AR-SVs. And compared to the normal individuals, the expression of Serine/arginine-rich splicing factor 2(SRSF2) was higher and the expression of SRSF3 was lower in the GCs of patients with AR-SVs. More importantly, we found that the expression of SRSF2 was inhibited and that the expression of AR was decreased after the successful upregulation of miRNA-183, and testostrone (T) concentrations in the culture medium were increased. The results also showed that the expression of SRSF3 decreased when miRNA-124 was successfully upregulated, while the expression of AR significantly increased; however, the function of AR was also inhibited when T concentration in the culture medium was increased. This study has proved that SRSFs are regulated by corresponding miRNAs, and the altered expression of SRSFs interferenced the alternative splicing process of AR and ultimately decreased the function of AR, leading to the accumulation of androgens in the ovary.

References

1

Curi DD, Fonseca AM, Marcondes JA, et al. Metformin versus lifestyle changes in treating women with polycystic ovary syndrome. Gynecol Endocrinol. 2012;28(3):182-185.

2

Chakraborty P, Goswami SK, Rajani S, et al. Recurrent pregnancy loss in polycystic ovary syndrome: role of hyperhomocysteinemia and insulin resistance. PLoS One. 2013;8(5),e64446.

3

Azziz R, Carmina E, Dewailly D, et al. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an androgen excess society guideline. J Clin Endocrinol Metab. 2006;91(11):4237-4245.

4

Yang M, Du J, Lu D, et al. Increased expression of kindlin 2 in luteinized granulosa cells correlates with androgen receptor level in patients with polycystic ovary syndrome having hyperandrogenemia. Reprod Sci. 2014;21(6):696-703.

5

Rajender S, Carlus SJ, Bansal SK, et al. Androgen receptor CAG repeats length polymorphism and the risk of polycystic ovarian syndrome (PCOS). PLoS One. 2013;8(10), e75709.

6

Shang K, Jia X, Qiao J, Kang J, Guan Y. Endometrial abnormality in women with polycystic ovary syndrome. Reprod Sci. 2012;19(7):674-683.

7

Yu J, Zhai D, Hao L, et al. Cryptotanshinone reverses reproductive and metabolic disturbances in PCOS model rats via regulating the expression of CYP17 and AR. Evid Based Complement Alternat Med. 2014;2014,e670743.

8

Yang X, Zhang Y, Wu X, et al. Cryptotanshinone reverses reproductive and metabolic disturbances in prenatally androgenized rats via regulation of ovarian signaling mechanisms and androgen synthesis. Am J Physiol Regul Integr Comp Physiol. 2011;300(4):R869-R875.

9

Liu Z, Hao C, Song D, Zhang N, Bao H, Qu Q. Androgen receptor coregulator CTBP1-AS is associated with polycystic ovary syndrome in Chinese women: a preliminary study. Reprod Sci. 2015;22(7):829-837.

10

Wang F, Pan J, Liu Y, et al. Alternative splicing of the androgen receptor in polycystic ovary syndrome. Proc Natl Acad Sci USA. 2015;112(15):4743-4748.

11

Gómez ALI, Fiszbein A, Alló M, Schor IE, Kornblihtt AR. Connections between chromatin signatures and splicing. Wiley Interdiscip Rev RNA. 2013;4(1):77-91.

12

Munkley J, Livermore K, Rajan P, Elliott DJ. RNA splicing and splicing regulator changes in prostate cancer pathology. Hum Genet. 2017;136(9):1143-1154.

13

Skrdlant L, Stark JM, Lin RJ. Myelodysplasia-associated mutations in serine/arginine-rich splicing factor SRSF2 lead to alternative splicing of CDC25C. BMC Mol Biol. 2016;17(1),e18.

14

Zhou Z, Fu XD. Regulation of splicing by SR proteins and SR protein-specific kinases. Chromosoma. 2013;122(3):191-207.

15

Jacquenet S, Decimo D, Muriaux D, Darlix J. Dual effect of the SR proteins ASF/SF2, SC35 and 9G8 on HIV-1 RNA splicing and virion production. Retrovirology. 2005;2,e33.

16

Expert-Bezancon A, Sureau A, Durosay P, et al. hnRNP A1 and the SR proteins ASF/SF2 and SC35 have antagonistic functions in splicing of beta-tropomyosin exon 6B. J Biol Chem. 2004;279(37):38249-38259.

17

Zhu J, Mayeda A, Krainer AR. Exon identity established through differential antagonism between exonic splicing silencer-bound hnRNP A1 and enhancer-bound SR proteins. Mol Cell. 2001;8(6):1351-1361.

18

Pandit S, Zhou Y, Shiue L, Coutinho-Mansfield G, Li H. Genome-wide analysis reveals SR protein cooperation and competition in regulated splicing. Mol Cell. 2013;50(2):223-235.

19

Chen L, Luo C, Shen L, et al. SRSF1 prevents DNA damage and promotes tumorigenesis through regulation of DBF4B pre-mRNA splicing. Cell Rep. 2017;21(12):3406-3413.

20

Sterne-Weiler T. Loss of exon identity is a common mechanism of human inherited disease. Genome Res. 2011;21(10):1563-1571.

21

Roundtree IA, He C. Nuclear m(6)A reader YTHDC1 regulates mRNA splicing. Trends Genet. 2016;32(6):320-321.

22

Xiao W, Adhikari S, Dahal U, et al. Nuclear m(6)A reader YTHDC1 regulates mRNA splicing. Mol Cell. 2016;61(4):507-519.

23

Roth LW, McCallie B, Alvero R, Schoolcraft WB, Minjarez D, Katz-Jaffe MG. Altered microRNA and gene expression in the follicular fluid of women with polycystic ovary syndrome. J Assist Reprod Genet. 2014;31(3):355-362.

24

Li C, Chen L, Zhao Y, et al. Altered expression of miRNAs in the uterus from a letrozole-induced rat PCOS model. Gene. 2017;598:20-26.

25

Norman RJ, Dewailly D, Legro RS, Hickey TE. Polycystic ovary syndrome. Lancet. 2007;370(9588):685-697.

26

Hossain MM, Cao M, Wang Q, et al. Altered expression of miRNAs in a dihydrotestosterone-induced rat PCOS model. J Ovarian Res. 2013;6(1),e36.

27

Sirotkin AV, Lauková M, Ovcharenko D, Brenaut P, Mlyncek M. Identification of microRNAs controlling human ovarian cell proliferation and apoptosis. J Cell Physiol. 2010;223(1):49-56.

28

Sirotkin AV, Ovcharenko D, Grossmann R, Lauková M, Mlyncek M. Identification of microRNAs controlling human ovarian cell steroidogenesis via a genome-scale screen. J Cell Physiol. 2009;219(2):415-420.

29

Kuokkanen S, Chen B, Ojalvo L, Benard L, Santoro N, Pollard JW. Genomic profiling of microRNAs and messenger RNAs reveals hormonal regulation in microRNA expression in human endometrium. Biol Reprod. 2010;82(4):791-801.

30

Beuzeboc P. Words of wisdom. Re: rapid induction of androgen receptor splice variants by androgen deprivation in prostate cancer. Eur Urol. 2014;66(6):1189-1190.

31

Nakazawa M, Antonarakis ES. Androgen receptor splice variants in the era of enzalutamide and abiraterone. Hormones Cancer. 2014;5(5):265-273.

32

Kedzierska H. Decreased expression of SRSF2 splicing factor inhibits apoptotic pathways in renal cancer. Int J Molec Sci. 2016;17(10),e1598.

33
Disease-associated mutation in SRSF2 misregulates splicing by altering RNA-binding affinities. Proc Nat Acad Sci. 2015;112(34):E4726-E4734.
34

Ouyang Y. Clinical significance of CSF3R, SRSF2 and SETBP1 mutations in chronic neutrophilic leukemia and chronic myelomonocytic leukemia. Oncotarget. 2017;8(13):20834-20841.

35

Yang J, AUID- Oho. The prognostic implication of SRSF2 mutations in chinese patients with acute myeloid leukemia. Tumor Biol. 2016;37(8):10107-10114.

36

Edmond V, Merdzhanova G, Gout S, Brambilla E, Gazzeri S, Eymin B. A new function of the splicing factor SRSF2 in the control of E2F1-mediated cell cycle progression in neuroendocrine lung tumors. Cell Cycle. 2013;12(8):1267-1278.

37

O'Neill S, Larsen MB, Gregersen S, Hermansen K, O'Driscoll L. miR-758-3p: a blood-based biomarker that's influence on the expression of CERP/ABCA1 may contribute to the progression of obesity to metabolic syndrome. Oncotarget. 2018;9(10):9379-9390.

38

Higuchi F, Uchida S, Yamagata H, et al. Hippocampal MicroRNA-124 enhances chronic stress resilience in mice. J Neurosci. 2016;36(27):7253-7267.

39

Liu S, Zhang X, Shi C, et al. Altered microRNAs expression profiling in cumulus cells from patients with polycystic ovary syndrome. J Transl Med. 2015;13,e238.

40

Zarrilli F, Amato F, Morgillo CM, et al. Peptide nucleic acids as miRNA target protectors for the treatment of cystic fibrosis. Molecules. 2017;22(7),e1144.

41

Bernardo BC, Ooi JY, Matsumoto A, et al. Sex differences in response to miRNA-34a therapy in mouse models of cardiac disease: identification of sex-, disease- and treatment-regulated miRNAs. J Physiol. 2016;594(20):5959-5974.

42

Reid G, Kao SC, Pavlakis N, et al. Clinical development of TargomiRs, a miRNA mimic-based treatment for patients with recurrent thoracic cancer. Epigenomics. 2016;8(8):1079-1085.

43

Zhang L, Yang X, Lv Y, et al. Cytosolic co-delivery of miRNA-34a and docetaxel with core-shell nanocarriers via caveolae-mediated pathway for the treatment of metastatic breast cancer. Sci Rep. 2017;7,46186.

44

Lin Y, Ge X, Wen Y, et al. MiRNA-145 increases therapeutic sensibility to gemcitabine treatment of pancreatic adenocarcinoma cells. Oncotarget. 2016;7(43):70857-70868.

Genes & Diseases
Pages 94-109
Cite this article:
Luo J, Ye H, Hao L, et al. SRSFs mediate the function of AR in the ovarian granulosa cells of patients with PCOS. Genes & Diseases, 2021, 8(1): 94-109. https://doi.org/10.1016/j.gendis.2019.09.005

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Received: 20 April 2019
Revised: 26 August 2019
Accepted: 04 September 2019
Published: 17 September 2019
© 2019, 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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