AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
Powered by AMiner. Clicking this button will take you away from SciOpen.
Home Cancer Biology & Medicine Article
PDF (1.6 MB)
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript AI Chat Paper
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Original Article | Open Access

LncRNA HIF1A-AS2 accelerates malignant phenotypes of renal carcinoma by modulating miR-30a-5p/SOX4 axis as a ceRNA

Mingwei Chen1, Xuedong Wei1, Xiu Shi2, Le Lu1, Guangbo Zhang1,3, Yuhua Huang1, Jianquan Hou1 ( )
Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Jiangsu Key Laboratory of Clinical Immunology, Soochow University, Jiangsu Key Laboratory of Gastrointestinal Tumor Immunology, Suzhou 215006, China
Show Author Information

Abstract

Objective

Several reports have proposed that lncRNAs, as potential biomarkers, participate in the progression and growth of malignant tumors. HIF1A-AS2 is a novel lncRNA and potential biomarker, involved in the genesis and development of carcinomas. However, the molecular mechanism of HIF1A-AS2 in renal carcinoma is unclear.

Methods

The relative expression levels of HIF1A-AS2 and miR-30a-5p were detected using RT-qPCR in renal carcinoma tissues and cell lines. Using loss-of-function and overexpression, the biological effects of HIF1A-AS2 and miR-30a-5p in kidney carcinoma progression were characterized. Dual luciferase reporter gene analysis and Western blot were used to detect the potential mechanism of HIF1A-AS2 in renal carcinomas.

Results

HIF1A-AS2 was upregulated in kidney carcinoma tissues when compared with para-carcinoma tissues (P < 0.05). In addition, tumor size, tumor node mestastasis stage and differentiation were identified as being closely associated with HIF1A-AS2 expression (P < 0.05). Knockdown or overexpression of HIF1A-AS2 either restrained or promoted the malignant phenotype and WNT/β-catenin signaling in renal carcinoma cells (P < 0.05). MiR-30a-5p was downregulated in renal cancers and partially reversed HIF1A-AS2 functions in malignant renal tumor cells. HIF1A-AS2 acted as a microRNA sponge that actively regulated the relative expression of SOX4 in sponging miR-30a-5p and subsequently increased the malignant phenotypes of renal carcinomas. HIF1A-AS2 showed a carcinogenic effect and miR-30a-5p acted as an antagonist of the anti-oncogene effects in the pathogenesis of renal carcinomas.

Conclusions

The HIF1A-AS2-miR-30a-5p-SOX4 axis was associated with the malignant progression and development of renal carcinoma. The relative expression of HIF1A-AS2 was negatively correlated with the expression of miR-30a-5p, and was closely correlated with SOX4 mRNA levels in renal cancers.

Keywords

ceRNASOX4HIF1A-AS2miR-30a-5pkidney carcinoma

References

1

Barthel FP, Johnson KC, Varn FS, Moskalik AD, Tanner G, Kocakavuk E, et al. Longitudinal molecular trajectories of diffuse glioma in adults. Nature. 2019; 576: 112-20.
Crossref Google Scholar
2

Moreno-Rubio J, Ponce S, Álvarez R, Olmedo ME, Falagan S, Mielgo X, et al. Clinical-pathological and molecular characterization of long-term survivors with advanced non-small cell lung cancer. Cancer Biol Med. 2020; 17: 444-57.
Crossref Google Scholar
3

Yan C, Chang J, Song X, Yan F, Yu W, An Y, et al. Memory stem T cells generated by Wnt signaling from blood of human renal clear cell carcinoma patients. Cancer Biol Med. 2019; 16: 109-24.
Crossref Google Scholar
4

Rose KM, Navaratnam AK, Faraj KS, Abdul-Muhsin HM, Syal A, Elias L, et al. Comparison of open and robot assisted radical nephrectomy with level Ⅰ and Ⅱ inferior vena cava tumor thrombus: the mayo clinic experience. Urology. 2020; 136: 152-7.
Crossref Google Scholar
5

Clark DJ, Dhanasekaran SM, Petralia F, Pan J, Song X, Hu Y, et al. Integrated proteogenomic characterization of clear cell renal cell carcinoma. Cell. 2020; 180: 207.
Crossref Google Scholar
6

Zhu H, Wang S, Shen H, Zheng X, Xu X. SP1/AKT/FOXO3 signaling is involved in miR-362-3p-mediated inhibition of cell-cycle pathway and EMT progression in renal cell carcinoma. Front Cell Dev Biol. 2020; 8: 297.
Crossref Google Scholar
7

Gargalionis AN, Sarlani E, Stofas A, Malakou LS, Adamopoulos C, Bamias A, et al. Polycystin-1 induces activation of the PI3K/AKT/mTOR pathway and promotes angiogenesis in renal cell carcinoma. Cancer Lett. 2020; 489: 135-43.
Crossref Google Scholar
8

Miao D, Margolis CA, Gao W, Voss MH, Li W, Martini DJ, et al. Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma. Science. 2018; 359: 801-6.
Crossref Google Scholar
9

He A, He S, Huang C, Chen Z, Wu Y, Gong Y, et al. MTDH promotes metastasis of clear cell renal cell carcinoma by activating SND1-mediated ERK signaling and epithelial-mesenchymal transition. Aging (Albany NY). 2020; 12: 1465-87.
Crossref Google Scholar
10

Chow PM, Liu SH, Chang YW, Kuo KL, Lin WC, Huang KH. The covalent CDK7 inhibitor THZ1 enhances temsirolimus-induced cytotoxicity via autophagy suppression in human renal cell carcinoma. Cancer Lett. 2020; 471: 27-37.
Crossref Google Scholar
11

Hamilton MJ, Young M, Jang K, Sauer S, Neang VE, King AT, et al. HOTAIRM1 lncRNA is downregulated in clear cell renal cell carcinoma and inhibits the hypoxia pathway. Cancer Lett. 2020; 472: 50-8.
Crossref Google Scholar
12

Wang C, Chen Y, Chen K, Zhang L. Long noncoding RNA LINC01134 promotes hepatocellular carcinoma metastasis via activating AKT1S1 and NF-κB signaling. Front Cell Dev Biol. 2020; 8: 429.
Crossref Google Scholar
13

Chen Y, Du H, Bao L. LncRNA PVT1 promotes ovarian cancer progression by silencing miR-214. Cancer Biol Med. 2018; 15: 238-50.
Crossref Google Scholar
14

Gong T, Li Y, Feng L, Fang M, Dai G, Huang X, et al. CASC21, a FOXP1 induced long non-coding RNA, promotes colorectal cancer growth by regulating CDK6. Aging (Albany NY). 2020; 12: 12086-106.
Crossref Google Scholar
15

Cho SW, Xu J, Sun R, Mumbach MR, Carter AC, Chen YG, et al. Promoter of lncRNA Gene HIF1A-AS2 is a tumor-suppressor DNA boundary element. Cell. 2018; 173: 1398-412.e22.
Crossref Google Scholar
16

Lü G, Li L, Wang B, Kuang L. LINC00623/miR-101/HRAS axis modulates IL-1 β-mediated ECM degradation, apoptosis and senescence of osteoarthritis chondrocytes. Aging (Albany NY). 2020; 12: 3218-37.
Crossref Google Scholar
17

Chu Y, Liu Z, Liu J, Yu L, Zhang D, Pei F. Characterization of lncRNA-perturbed TLR-signaling network identifies novel lncRNA prognostic biomarkers in colorectal cancer. Front Cell Dev Biol. 2020; 8: 503.
Crossref Google Scholar
18

Yu X, Ye X, Lin H, Feng N, Gao S, Zhang X, et al. Knockdown of long non-coding RNA inhibits autophagy in lung cancer. Cancer Biol Med. 2018; 15: 228-37.
Crossref Google Scholar
19

Jackson R, Kroehling L, Khitun A, Bailis W, Jarret A, York AG, et al. The translation of non-canonical open reading frames controls mucosal immunity. Nature. 2018; 564: 434-8. s
Crossref Google Scholar
20

Li J, Zhuang C, Liu Y, Chen M, Chen Y, Chen Z, et al. Synthetic tetracycline-controllable shRNA targeting long non-coding RNA HOXD-AS1 inhibits the progression of bladder cancer. J Exp Clin Cancer Res. 2016; 35: 99.
Crossref Google Scholar
21

Xu J, Lu Y, Liu Q, Xia A, Zhao J, Xu X, et al. Long noncoding RNA GMAN promotes hepatocellular carcinoma progression by interacting with eIF4B. Cancer Lett. 2020; 473: 1-12.
Crossref Google Scholar
22

Sarropoulos I, Marin R, Cardoso-Moreira M. Developmental dynamics of lncRNAs across mammalian organs and species. Nature. 2019; 571: 510-4.
Crossref Google Scholar
23

Zhang M, Tang M, Wu Q, Wang Z, Chen Z, Ding H, et al. LncRNA DANCR attenuates brain microvascular endothelial cell damage induced by oxygen-glucose deprivation through regulating of miR-33a-5p/XBP1s. Aging (Albany NY). 2020; 12: 1778-91.
Crossref Google Scholar
24

Qi Y, Wu H, Mai C, Lin H, Shen J, Zhang X, et al. LncRNA-MIAT-mediated miR-214-3p silencing is responsible for IL-17 production and cardiac fibrosis in diabetic cardiomyopathy. Front Cell Dev Biol. 2020; 8: 243.
Crossref Google Scholar
25

Feng Y, Hu S, Li L, Zhang S, Liu J, Xu X, et al. LncRNA NR-104098 inhibits AML proliferation and induces differentiation through repressing EZH2 transcription by interacting with E2F1. Front Cell Dev Biol. 2020; 8: 142.
Crossref Google Scholar
26

Peng PH, Chieh-Yu Lai J, Hsu KW, Wu KJ. Hypoxia-induced lncRNA RP11-390F4.3 promotes epithelial-mesenchymal transition (EMT) and metastasis through upregulating EMT regulators. Cancer Lett. 2020; 483: 35-45.
Crossref Google Scholar
27

Chen M, Li J, Zhuang C. Increased lncRNA ABHD11-AS1 represses the malignant phenotypes of bladder cancer. Oncotarget. 2017; 8: 28176-86.
Crossref Google Scholar
28

Zhang W, Liu Y, Fu Y, Han W, Xu H, Wen L, et al. Long non-coding RNA LINC00160 functions as a decoy of microRNA-132 to mediate autophagy and drug resistance in hepatocellular carcinoma via inhibition of PIK3R3. Cancer Lett. 2020; 478: 22-33.
Crossref Google Scholar
29

Chen WM, Huang MD, Kong R, Xu TP, Zhang EB, Xia R, et al. Antisense long noncoding RNA HIF1A-AS2 is upregulated in gastric cancer and associated with poor prognosis. Dig Dis Sci. 2015; 60: 1655-62.
Crossref Google Scholar
30

Jiang YZ, Liu YR, Xu XE, Jin X, Hu X, Yu KD, et al. Transcriptome analysis of triple-negative breast cancer reveals an integrated mRNA-lncRNA signature with predictive and prognostic value. Cancer Res. 2016; 76: 2105-14.
Crossref Google Scholar
31

Guo X, Lee S. The inhibitive effect of sh-HIF1A-AS2 on the proliferation, invasion, and pathological damage of breast cancer via targeting miR-548c-3p through regulating HIF-1α/VEGF pathway in vitro and vivo. Onco Targets Ther. 2019; 12: 825-34.
Crossref Google Scholar
32

Liu M, Xing LQ, Liu YJ. A three-long noncoding RNA signature as a diagnostic biomarker for differentiating between triple-negative and non-triple-negative breast cancers. Medicine. 2017; 96: e6222.
Crossref Google Scholar
33

Wang Y, Zhang G. HIF1A-AS2 predicts poor prognosis and regulates cell migration and invasion in triple-negative breast cancer. J Cell Biochem. 2019; 120: 10513-8.
Crossref Google Scholar
34

Chen M, Zhuang C, Liu Y, Li J, Dai F, Xia M, et al. Tetracycline-inducible shRNA targeting antisense long non-coding RNA HIF1A-AS2 represses the malignant phenotypes of bladder cancer. Cancer Lett. 2016; 376: 155-64.
Crossref Google Scholar
35

Chen X, Liu M, Meng F, Sun B, Jin X, Jia C, et al. The long noncoding RNA HIF1A-AS2 facilitates cisplatin resistance in bladder cancer. J Cell Biochem. 2019; 120: 243-52.
Crossref Google Scholar
36

Mineo M, Ricklefs F, Rooj AK, Lyons SM, Ivanov P, Ansari KI, et al. The long non-coding RNA HIF1A-AS2 facilitates the maintenance of mesenchymal glioblastoma stem-like cells in hypoxic niches. J Cell Rep. 2016; 15: 2500-9.
Crossref Google Scholar
37

Lin J, Shi Z, Yu Z. LncRNA HIF1A-AS2 positively affects the progression and EMT formation of colorectal cancer through regulating miR-129-5p and DNMT3A. Biomed Pharmacother. 2018; 98: 433-9.
Crossref Google Scholar
38

Wu R, Ruan J, Sun Y, Liu M, Sha Z, Fan C, et al. Long non-coding RNA HIF1A-AS2 facilitates adipose-derived stem cells (ASCs) osteogenic differentiation through miR-665/IL6 axis via PI3K/Akt signaling pathway. Stem Cell Res Ther. 2018; 9: 348.
Crossref Google Scholar
39

Zhang Y, Zhang L, Wang Y, Ding H, Xue S, Yu H, et al. KCNQ1OT1, HIF1A-AS2 and APOA1-AS are promising novel biomarkers for diagnosis of coronary artery disease. Clin Exp Pharmacol Physiol. 2019; 46: 635-42.
Crossref Google Scholar
40

Wu D, Yang N, Xu Y, Wang S, Zhang Y, Sagnelli M, et al. lncRNA HIF1A antisense RNA 2 modulates trophoblast cell invasion and proliferation through upregulating PHLDA1 expression. Mol Ther Nucleic Acids. 2019; 16: 605-15.
Crossref Google Scholar
41

Lin H, Zhao Z, Hao Y, He J, He J. Long noncoding RNA HIF1A-AS2 facilitates cell survival and migration by sponging miR-33b-5p to modulate SIRT6 expression in osteosarcoma. Biochem Cell Biol. 2020;98:284-92.
Crossref Google Scholar
42

Zhang JW, Wang X, Li GC, Wang D, Han S, Zhang YD, et al. MiR-30a-5p promotes cholangiocarcinoma cell proliferation through targeting SOCS3. J Cancer. 2020; 11: 3604-14.
Crossref Google Scholar
43

Zhang Y, Ma L, Wang C, Wang L, Guo Y, Wang G. Long noncoding RNA LINC00461 induced osteoarthritis progression by inhibiting miR-30a-5p. Aging (Albany NY). 2020; 12: 4111-23.
Crossref Google Scholar
44

Li X, Liu J, Liu M, Xia C, Zhao Q. The Lnc LINC00461/miR-30a-5p facilitates progression and malignancy in non-small cell lung cancer via regulating ZEB2. Cell Cycle. 2020; 19: 825-36.
Crossref Google Scholar
45

Li J, Xu X, Wei C, Liu L, Wang T. Long noncoding RNA NORAD regulates lung cancer cell proliferation, apoptosis, migration, and invasion by the miR-30a-5p/ADAM19 axis. Int J Clin Exp Pathol. 2020; 13: 1-13.
Google Scholar
46

Wu W, Zhao Y, Gao E, Li Y, Guo X, Zhao T, etal. LncRNA DLEU2 accelerates the tumorigenesis and invasion of non-small cell lung cancer by sponging miR-30a-5p. J Cell Mol Med. 2020; 24: 441-50.
Crossref Google Scholar
47

Tang M, Zhou J, You L, Cui Z, Zhang H. LIN28B/IRS1 axis is targeted by miR-30a-5p and promotes tumor growth in colorectal cancer. J Cell Biochem. 2020; 121: 3720-9.
Crossref Google Scholar
48

Li J, Zhao LM, Zhang C, Li M, Gao B, Hu XH, et al. The lncRNA FEZF1-AS1 Promotes the progression of colorectal cancer through regulating OTX1 and targeting miR-30a-5p. Oncol Res. 2020; 28: 51-63.
Crossref Google Scholar
49

Saleh AD, Cheng H, Martin SE, Si H, Ormanoglu P, Carlson S, et al. Integrated genomic and functional microRNA analysis identifies miR-30-5p as a tumor suppressor and potential therapeutic nanomedicine in head and neck cancer. Clin Cancer Res. 2019; 25: 2860-73.
Crossref Google Scholar
50

Han C, Xu B, Zhou L, Li L, Lu C, Yu GP, et al. LINC02738 Participates in the Development of Kidney Cancer Through the miR-20b/Sox4 Axis. Onco Targets Ther. 2020;13:10185-96.
Crossref Google Scholar
51

Liu L, Yan Y, Zhang G, Chen C, Shen W, Xing P, et al. Knockdown of LINC01694 inhibits growth of gallbladder cancer cells via miR-340-5p/Sox4. Biosci Rep. 2020; 40: BSR20194444.
Crossref Google Scholar
52

Ying X, Zhang W, Fang M, Wang C, Han L, Yang C. LncRNA SNHG5 regulates SOX4 expression through competitive binding to miR-489-3p in acute myeloid leukemia. Inflamm Res. 2020; 69: 607-18.
Crossref Google Scholar
53

Zhang J, Zhang K, Hou Y. Long non-coding RNA NNT-AS1 knockdown represses the progression of gastric cancer via modulating the miR-142-5p/SOX4/Wnt/β-catenin signaling pathway. Mol Med Rep. 2020;22:687-96.
Crossref Google Scholar
54

Chen H, Liu T, Ouyang H, Lin S, Zhong H, Zhang H, et al. Upregulation of FTX Promotes Osteosarcoma Tumorigenesis by Increasing SOX4 Expression via miR-214-5p. Onco Targets Ther. 2020;13:7125-36.
Crossref Google Scholar
55

Zhao J, Bai X, Feng C, Shang X, Xi Y. Long non-coding RNA HCP5 facilitates cell invasion and epithelial-mesenchymal transition in oral squamous cell carcinoma by miR-140-5p/SOX4 axis. Cancer Manag Res. 2019; 11: 10455-62.
Crossref Google Scholar
56

Li L, Wang M, Mei Z, Cao W, Yang Y, Wang Y, et al. LncRNAs HIF1A-AS2 facilitates the up-regulation of HIF-1α by sponging to miR-153-3p, whereby promoting angiogenesis in HUVECs in hypoxia. Biomed Pharmacother. 2017; 96: 165-72.
Crossref Google Scholar
Cancer Biology & Medicine
Volume 18 Issue 2,
May 2021
Pages 587-603
DOI: 10.20892/j.issn.2095-3941.2020.0209
Cite this article:
Chen M, Wei X, Shi X, et al. LncRNA HIF1A-AS2 accelerates malignant phenotypes of renal carcinoma by modulating miR-30a-5p/SOX4 axis as a ceRNA. Cancer Biology & Medicine, 2021, 18(2): 587-603. https://doi.org/10.20892/j.issn.2095-3941.2020.0209

67

Views

0

Downloads

13

Crossref

18

Web of Science

17

Scopus

Altmetrics
Received: 04 May 2020
Accepted: 21 August 2020
Published: 01 May 2021
©2021 Cancer Biology & Medicine.

Creative Commons Attribution-NonCommercial 4.0 International License
Return