miR‑152‑mediated MKK7 downregulation is attenuated by MYCNOS in ovarian adenocarcinoma

Zhang,Guifang; Zheng,Dan; Chen,Xiaoqing; Li,Li; Yu,Jingrong

doi:10.3892/ol.2021.13102

miR‑152‑mediated MKK7 downregulation is attenuated by MYCNOS in ovarian adenocarcinoma

Authors:
- Guifang Zhang
- Dan Zheng
- Xiaoqing Chen
- Li Li
- Jingrong Yu
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Affiliations: Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, P.R. China, Day Operation Center, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi 330003, P.R. China, Department of Oncology, The Fourth Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330003, P.R. China
Published online on: October 20, 2021 https://doi.org/10.3892/ol.2021.13102
Article Number: 841
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

MYCN opposite strand (MYCNOS) acts as an oncogenic long non‑coding RNA in liver cancer. However, its role in other cancer types is unknown. The aim of the present study was to investigate the function of MYCNOS in ovarian adenocarcinoma (OA). MYCNOS expression in OA was determined using reverse transcription‑quantitative PCR (RT‑qPCR), and its prognostic value for OA was evaluated in a 5‑year follow‑up study. The predicted interaction between MYCNOS and microRNA (miR)‑152 was confirmed using a dual luciferase reporter assay. The association between MYCNOS and miR‑152 was also analyzed in overexpression experiments. The effects of MYCNOS and miR‑152 on mitogen‑activated protein kinase kinase 7 (MKK7) expression were explored using RT‑qPCR and western blotting. Cell proliferation was analyzed using a Cell Counting Kit‑8 assay. MYCNOS expression was found to be upregulated in OA and predicted poor survival. In addition, MYCNOS was predicted to interact with miR‑152, and a dual luciferase assay confirmed this interaction. However, MYCNOS and miR‑152 overexpression did not affect their mutual expression levels. MYCNOS overexpression upregulated MKK7, a target of miR‑152. Cell proliferation increased following simultaneous MYCNOS and MKK7 overexpression, but was reduced following miR‑152 overexpression. Moreover, MYCNOS overexpression attenuated the effects of miR‑152 overexpression. In conclusion, MYCNOS may act by sponging miR‑152 to upregulate MKK7 expression in OA, thereby promoting cell proliferation.

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1	Jayson GC, Kohn EC, Kitchener HC and Ledermann JA: Ovarian cancer. Lancet. 384:1376–1388. 2014. View Article : Google Scholar : PubMed/NCBI
2	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
3	Vaughan S, Coward JI, Bast RC Jr, Berchuck A, Berek JS, Brenton JD, Coukos G, Crum CC, Drapkin R, Etemadmoghadam D, et al: Rethinking ovarian cancer: Recommendations for improving outcomes. Nat Rev Cancer. 11:719–725. 2011. View Article : Google Scholar : PubMed/NCBI
4	Torre LA, Trabert B, DeSantis CE, Miller KD, Samimi G, Runowicz CD, Gaudet MM, Jemal A and Siegel RL: Ovarian cancer statistics, 2018. CA Cancer J Clin. 68:284–296. 2018. View Article : Google Scholar : PubMed/NCBI
5	La Vecchia C: Ovarian cancer: Epidemiology and risk factors. Eur J Cancer Prev. 26:55–62. 2017. View Article : Google Scholar : PubMed/NCBI
6	Hunn J and Rodriguez GC: Ovarian cancer: Etiology, risk factors, and epidemiology. Clin Obstet Gynecol. 55:3–23. 2012. View Article : Google Scholar : PubMed/NCBI
7	Sapiezynski J, Taratula O, Rodriguez-Rodriguez L and Minko T: Precision targeted therapy of ovarian cancer. J Control Release. 243:250–268. 2016. View Article : Google Scholar : PubMed/NCBI
8	Duan P, Fan L, Gao Q, Silwal BM, Ren M, Shen Y and Qu W: Targeted Therapy of Ovarian Cancer with Angiogenesis Inhibitors. Curr Drug Targets. 18:1171–1178. 2017. View Article : Google Scholar : PubMed/NCBI
9	Kim A, Ueda Y, Naka T and Enomoto T: Therapeutic strategies in epithelial ovarian cancer. J Exp Clin Cancer Res. 31:142012. View Article : Google Scholar : PubMed/NCBI
10	Lee YT, Tan YJ and Oon CE: Molecular targeted therapy: Treating cancer with specificity. Eur J Pharmacol. 834:188–196. 2018. View Article : Google Scholar : PubMed/NCBI
11	Deb B, Uddin A and Chakraborty S: miRNAs and ovarian cancer: An overview. J Cell Physiol. 233:3846–3854. 2018. View Article : Google Scholar : PubMed/NCBI
12	Tripathi MK, Doxtater K, Keramatnia F, Zacheaus C, Yallapu MM, Jaggi M and Chauhan SC: Role of lncRNAs in ovarian cancer: Defining new biomarkers for therapeutic purposes. Drug Discov Today. 23:1635–1643. 2018. View Article : Google Scholar : PubMed/NCBI
13	Yu J, Ou Z, Lei Y, Chen L, Su Q and Zhang K: lncRNA MYCNOS facilitates proliferation and invasion in hepatocellular carcinoma by regulating miR-340. Hum Cell. 33:148–158. 2020. View Article : Google Scholar : PubMed/NCBI
14	Liu H, Zhang M, Shi M, Zhang T, Zhang Z, Cui Q, Yang S and Li Z: A Survival-Related Competitive Endogenous RNA Network of Prognostic lncRNAs, miRNAs, and mRNAs in Wilms Tumor. Front Oncol. 11:6084332021. View Article : Google Scholar : PubMed/NCBI
15	Nakagawa K, Sugahara M, Yamasaki T, Kajiho H, Takahashi S, Hirayama J, Minami Y, Ohta Y, Watanabe T, Hata Y, et al: Filamin associates with stress signalling kinases MKK7 and MKK4 and regulates JNK activation. Biochem J. 427:237–245. 2010. View Article : Google Scholar : PubMed/NCBI
16	Wada T, Joza N, Cheng HY, Sasaki T, Kozieradzki I, Bachmaier K, Katada T, Schreiber M, Wagner EF, Nishina H, et al: MKK7 couples stress signalling to G2/M cell-cycle progression and cellular senescence. Nat Cell Biol. 6:215–226. 2004. View Article : Google Scholar : PubMed/NCBI
17	Edge SB and Compton CC: The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 17:1471–1474. 2010. View Article : Google Scholar : PubMed/NCBI
18	Chu C, Quinn J and Chang HY: Chromatin isolation by RNA purification (ChIRP). J Vis Exp. 61:39122012.PubMed/NCBI
19	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 : PubMed/NCBI
20	Lutz AM, Willmann JK, Drescher CW, Ray P, Cochran FV, Urban N and Gambhir SS: Early diagnosis of ovarian carcinoma: Is a solution in sight? Radiology. 259:329–345. 2011. View Article : Google Scholar : PubMed/NCBI
21	Shi X, Sun M, Liu H, Yao Y and Song Y: Long non-coding RNAs: A new frontier in the study of human diseases. Cancer Lett. 339:159–166. 2013. View Article : Google Scholar : PubMed/NCBI
22	Qiu MT, Hu JW, Yin R and Xu L: Long noncoding RNA: An emerging paradigm of cancer research. Tumour Biol. 34:613–620. 2013. View Article : Google Scholar : PubMed/NCBI
23	Vadie N, Saayman S, Lenox A, Ackley A, Clemson M, Burdach J, Hart J, Vogt PK and Morris KV: MYCNOS functions as an antisense RNA regulating MYCN. RNA Biol. 12:893–899. 2015. View Article : Google Scholar : PubMed/NCBI
24	O'Brien EM, Selfe JL, Martins AS, Walters ZS and Shipley JM: The long non-coding RNA MYCNOS-01 regulates MYCN protein levels and affects growth of MYCN-amplified rhabdomyosarcoma and neuroblastoma cells. BMC Cancer. 18:2172018. View Article : Google Scholar : PubMed/NCBI
25	Malizia AP and Wang DZ: MicroRNAs in cardiomyocyte development. Wiley Interdiscip Rev Syst Biol Med. 3:183–190. 2011. View Article : Google Scholar : PubMed/NCBI
26	Kovalchuk O, Filkowski J, Meservy J, Ilnytskyy Y, Tryndyak VP, Chekhun VF and Pogribny IP: Involvement of microRNA-451 in resistance of the MCF-7 breast cancer cells to chemotherapeutic drug doxorubicin. Mol Cancer Ther. 7:2152–2159. 2008. View Article : Google Scholar : PubMed/NCBI
27	Huang J, Wang Y, Guo Y and Sun S: Down-regulated microRNA-152 induces aberrant DNA methylation in hepatitis B virus-related hepatocellular carcinoma by targeting DNA methyltransferase 1. Hepatology. 52:60–70. 2010. View Article : Google Scholar : PubMed/NCBI
28	Zhou X, Zhao F, Wang ZN, Song YX, Chang H, Chiang Y and Xu HM: Altered expression of miR-152 and miR-148a in ovarian cancer is related to cell proliferation. Oncol Rep. 27:447–454. 2012.PubMed/NCBI
29	Xiang Y, Ma N, Wang D, Zhang Y, Zhou J, Wu G, Zhao R, Huang H, Wang X, Qiao Y, et al: miR-152 and miR-185 co-contribute to ovarian cancer cells cisplatin sensitivity by targeting DNMT1 directly: A novel epigenetic therapy independent of decitabine. Oncogene. 33:378–386. 2014. View Article : Google Scholar : PubMed/NCBI
30	Wallace MC, Preen DB, Short MW, Adams LA and Jeffrey GP: Hepatocellular carcinoma in Australia 1982–2014: Increasing incidence and improving survival. Liver Int. 39:522–530. 2019. View Article : Google Scholar : PubMed/NCBI
31	You W, Zhang X, Ji M, Yu Y, Chen C, Xiong Y, Liu Y, Sun Y, Tan C, Zhang H, et al: miR-152-5p as a microRNA passenger strand special functions in human gastric cancer cells. Int J Biol Sci. 14:644–653. 2018. View Article : Google Scholar : PubMed/NCBI