Silencing of the long noncoding RNA LINC01132 alleviates the oncogenicity of epithelial ovarian cancer by regulating the microRNA‑431‑5p/SOX9 axis

Zhu,Wei; Xiao,Xiangming; Chen,Jinqin

doi:10.3892/ijmm.2021.4984

Silencing of the long noncoding RNA LINC01132 alleviates the oncogenicity of epithelial ovarian cancer by regulating the microRNA‑431‑5p/SOX9 axis

Authors:
- Wei Zhu
- Xiangming Xiao
- Jinqin Chen
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Affiliations: Department of Gynaecology and Obstetrics, Weifang People's Hospital, Weifang, Shandong 261401, P.R. China, Department of General Surgery, Weifang People's Hospital, Weifang, Shandong 261401, P.R. China
Published online on: June 15, 2021 https://doi.org/10.3892/ijmm.2021.4984
Article Number: 151
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

To date, the role of lncRNA long intergenic non‑protein‑coding RNA 1132 (LINC01132) expression in epithelial ovarian cancer (EOC) has not been explored. Thus, LINC01132 expression in EOC was assessed and the regulatory activity of LINC01132 on the malignant behaviours of EOC cells was investigated. Additionally, the molecular events that occurred downstream of LINC01132 in EOC cells were also revealed. In the present study, LINC01132 expression in EOC was verified by employing RT‑qPCR. The effects of LINC01132 on the aggressive behaviours of EOC cells were revealed utilizing multiple functional experiments. The targeting interaction among LINC01132, microRNA‑431‑5p (miR‑431‑5p) and SRY‑box 9 (SOX9) was demonstrated by RNA immunoprecipitation and luciferase reporter assay. Herein, LINC01132 was overexpressed in EOC and was significantly associated with poor patient prognosis. Functionally, cell experiments revealed that LINC01132 depletion produced cancer‑suppressive effects in EOC cells and regulated cell proliferation, migration, invasion and apoptosis in vitro. Additionally, the loss of LINC01132 attenuated tumour growth in vivo. Mechanistically, LINC01132 acted as a competing endogenous RNA by sequestering miR‑431‑5p and consequently overexpressing SOX9 in EOC cells, forming a LINC01132/miR‑431‑5p/SOX9 axis. In rescue experiments, miR‑431‑5p inhibition or SOX9 reintroduction eliminated the anti‑tumour effects of LINC01132 silencing on the pathological behaviours of EOC cells. Generally, LINC01132 exhibited oncogenic activities in EOC cells by regulating the outcome of the miR‑431‑5p/SOX9 axis, providing an effective target for EOC diagnosis, therapy and prognosis evaluation.

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1	Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI
2	Allemani C, Matsuda T, Di Carlo V, Harewood R, Matz M, Nikšić M, Bonaventure A, Valkov M, Johnson CJ, Estève J, et al: Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): Analysis of individual records for 37,513,025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet. 391:1023–1075. 2018. View Article : Google Scholar : PubMed/NCBI
3	Di Lorenzo G, Ricci G, Severini GM, Romano F and Biffi S: Imaging and therapy of ovarian cancer: Clinical application of nanoparticles and future perspectives. Theranostics. 8:4279–4294. 2018. View Article : Google Scholar : PubMed/NCBI
4	Kuroki L and Guntupalli SR: Treatment of epithelial ovarian cancer. BMJ. 371:m37732020. View Article : Google Scholar : PubMed/NCBI
5	Gourley C and Bookman MA: Evolving concepts in the management of newly diagnosed epithelial ovarian cancer. J Clin Oncol. 37:2386–2397. 2019. View Article : Google Scholar : PubMed/NCBI
6	Rojas V, Hirshfield KM, Ganesan S and Rodriguez-Rodriguez L: Molecular characterization of epithelial ovarian cancer: Implications for diagnosis and treatment. Int J Mol Sci. 17:21132016. View Article : Google Scholar
7	Sundar S, Neal RD and Kehoe S: Diagnosis of ovarian cancer. BMJ. 351:h44432015. View Article : Google Scholar : PubMed/NCBI
8	Nagano T and Fraser P: No-nonsense functions for long noncoding RNAs. Cell. 145:178–181. 2011. View Article : Google Scholar : PubMed/NCBI
9	Qiu L, Tang Q, Li G and Chen K: Long non-coding RNAs as biomarkers and therapeutic targets: Recent insights into hepato-cellular carcinoma. Life Sci. 191:273–282. 2017. View Article : Google Scholar : PubMed/NCBI
10	Wang Y, Zhang M and Zhou F: Biological functions and clinical applications of exosomal long non-coding RNAs in cancer. J Cell Mol Med. 24:11656–11666. 2020. View Article : Google Scholar : PubMed/NCBI
11	Pei C, Gong X and Zhang Y: LncRNA MALAT-1 promotes growth and metastasis of epithelial ovarian cancer via sponging microrna-22. Am J Transl Res. 12:6977–6987. 2020.PubMed/NCBI
12	Braga EA, Fridman MV, Moscovtsev AA, Filippova EA, Dmitriev AA and Kushlinskii NE: LncRNAs in ovarian cancer progression, metastasis, and main pathways: ceRNA and alternative mechanisms. Int J Mol Sci. 21:88552020. View Article : Google Scholar :
13	Wambecke A, Ahmad M, Lambert B, Joly F, Poulain L, Denoyelle C and Meryet-Figuiere M: The influence of long non-coding RNAs on the response to chemotherapy in ovarian cancer. Gynecol Oncol. 156:726–733. 2020. View Article : Google Scholar
14	Zeng S, Liu S, Feng J, Gao J and Xue F: Upregulation of lncRNA AB073614 functions as a predictor of epithelial ovarian cancer prognosis and promotes tumor growth in vitro and in vivo. Cancer Biomark. 24:421–428. 2019. View Article : Google Scholar : PubMed/NCBI
15	Wu W, Gao H, Li X, Zhu Y, Peng S, Yu J, Zhan G, Wang J, Liu N and Guo X: LncRNA TPT1-AS1 promotes tumorigenesis and metastasis in epithelial ovarian cancer by inducing TPT1 expression. Cancer Sci. 110:1587–1598. 2019. View Article : Google Scholar : PubMed/NCBI
16	Zhao J and Liu HR: Down-regulation of long noncoding RNA DLX6-AS1 defines good prognosis and inhibits proliferation and metastasis in human epithelial ovarian cancer cells via Notch signaling pathway. Eur Rev Med Pharmacol Sci. 23:3243–3252. 2019.PubMed/NCBI
17	Lu TX and Rothenberg ME: MicroRNA. J Allergy Clin Immunol. 141:1202–1207. 2018. View Article : Google Scholar :
18	Nguyen VHL, Yue C, Du KY, Salem M, O'Brien J and Peng C: The role of microRNAs in epithelial ovarian cancer metastasis. Int J Mol Sci. 21:70932020. View Article : Google Scholar :
19	Staicu CE, Predescu DV, Rusu CM, Radu BM, Cretoiu D, Suciu N, Crețoiu SM and Voinea SC: Role of microRNAs as clinical cancer biomarkers for ovarian cancer: A short overview. Cells. 9:1692020. View Article : Google Scholar :
20	Khan S, Ayub H, Khan T and Wahid F: MicroRNA biogenesis, gene silencing mechanisms and role in breast, ovarian and prostate cancer. Biochimie. 167:12–24. 2019. View Article : Google Scholar : PubMed/NCBI
21	Niu ZS, Wang WH, Dong XN and Tian LM: Role of long noncoding RNA-mediated competing endogenous RNA regulatory network in hepatocellular carcinoma. World J Gastroenterol. 26:4240–4260. 2020. View Article : Google Scholar : PubMed/NCBI
22	Weng W, Zhang Z, Huang W, Xu X, Wu B, Ye T, Shan Y, Shi K and Lin Z: Identification of a competing endogenous RNA network associated with prognosis of pancreatic adenocarcinoma. Cancer Cell Int. 20:2312020. View Article : Google Scholar : PubMed/NCBI
23	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar
24	Raspaglio G, Petrillo M, Martinelli E, Li Puma DD, Mariani M, De Donato M, Filippetti F, Mozzetti S, Prislei S, Zannoni GF, et al: Sox9 and Hif-2α regulate TUBB3 gene expression and affect ovarian cancer aggressiveness. Gene. 542:173–181. 2014. View Article : Google Scholar : PubMed/NCBI
25	Malki S, Bibeau F, Notarnicola C, Roques S, Berta P, Poulat F and Boizet-Bonhoure B: Expression and biological role of the prostaglandin D synthase/SOX9 pathway in human ovarian cancer cells. Cancer Lett. 255:182–193. 2007. View Article : Google Scholar : PubMed/NCBI
26	Xiao S, Li Y, Pan Q, Ye M, He S, Tian Q and Xue M: MiR-34c/SOX9 axis regulates the chemoresistance of ovarian cancer cell to cisplatin-based chemotherapy. J Cell Biochem. 120:2940–2953. 2019. View Article : Google Scholar
27	McCabe EM and Rasmussen TP: lncRNA involvement in cancer stem cell function and epithelial-mesenchymal transitions. Semin Cancer Biol. Dec 17–2020.Epub ahead of print. View Article : Google Scholar : PubMed/NCBI
28	Qian Y, Shi L and Luo Z: Long non-coding RNAs in cancer: Implications for diagnosis, prognosis, and therapy. Front Med ( Lausanne). 7:6123932020. View Article : Google Scholar
29	Chen S and Shen X: Long noncoding RNAs: Functions and mechanisms in colon cancer. Mol Cancer. 19:1672020. View Article : Google Scholar : PubMed/NCBI
30	Nikpayam E, Tasharrofi B, Sarrafzadeh S and Ghafouri-Fard S: The role of long non-coding RNAs in ovarian cancer. Iran Biomed J. 21:3–15. 2017. View Article : Google Scholar :
31	Tong L, Ao Y, Zhang H, Wang K, Wang Y and Ma Q: Long noncoding RNA NORAD is upregulated in epithelial ovarian cancer and its downregulation suppressed cancer cell functions by competing with miR-155-5p. Cancer Med. 8:4782–4791. 2019. View Article : Google Scholar : PubMed/NCBI
32	Zheng T, Qiu J, Li C, Lin X, Tang X and Hua K: Long noncoding RNA LINC00673 promotes the proliferation and metastasis of epithelial ovarian cancer by associating with opioid growth factor receptor. Onco Targets Ther. 12:6145–6156. 2019. View Article : Google Scholar : PubMed/NCBI
33	Qiu JJ, Lin XJ, Tang XY, Zheng TT, Zhang XY and Hua KQ: Long noncoding RNA TC0101441 induces epithelial-mesenchymal transition in epithelial ovarian cancer metastasis by downregulating KiSS1. Int J Cancer. 146:2588–2598. 2020. View Article : Google Scholar
34	Li W, Ma S, Bai X, Pan W, Ai L and Tan W: Long noncoding RNA WDFY3-AS2 suppresses tumor progression by acting as a competing endogenous RNA of microRNA-18a in ovarian cancer. J Cell Physiol. 235:1141–1154. 2020. View Article : Google Scholar
35	Gokulnath P, de Cristofaro T, Manipur I, Di Palma T, Soriano AA, Guarracino MR and Zannini M: Long non-coding RNA MAGI2-AS3 is a new player with a tumor suppressive role in high grade serous ovarian carcinoma. Cancers (Basel). 11. pp. 20082019, View Article : Google Scholar
36	Lin X, Tang X, Zheng T, Qiu J and Hua K: Long non-coding RNA AOC4P suppresses epithelial ovarian cancer metastasis by regulating epithelial-mesenchymal transition. J Ovarian Res. 13:452020. View Article : Google Scholar : PubMed/NCBI
37	Qu J, Li M, Zhong W and Hu C: Competing endogenous RNA in cancer: A new pattern of gene expression regulation. Int J Clin Exp Med. 8:17110–17116. 2015.
38	Yang L, Lv Q, Liu J, Qi S and Fu D: miR-431 regulates granulosa cell function through the IRS2/PI3K/AKT signaling pathway. J Reprod Dev. 66:231–239. 2020. View Article : Google Scholar : PubMed/NCBI