GATA6‑AS1 inhibits ovarian cancer cell proliferation and migratory and invasive abilities by sponging miR‑19a‑5p and upregulating TET2

Xu,Hua; Wang,Xiao; Zhang,Yinghong; Zheng,Wei; Zhang,Huijie

doi:10.3892/ol.2021.12979

GATA6‑AS1 inhibits ovarian cancer cell proliferation and migratory and invasive abilities by sponging miR‑19a‑5p and upregulating TET2

Authors:
- Hua Xu
- Xiao Wang
- Yinghong Zhang
- Wei Zheng
- Huijie Zhang
View Affiliations

Affiliations: Department of Obstetrics, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China, Department of Gynecology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China
Published online on: August 9, 2021 https://doi.org/10.3892/ol.2021.12979
Article Number: 718
Copyright : © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

GATA6 antisense RNA 1 (GATA6‑AS1) has been reported to be involved in the progression of several types of cancer. In the present study, the role of GATA6‑AS1 in ovarian cancer (OC) was explored. Reverse transcription quantitative PCR was used to detect the expression of GATA6‑AS1, microRNA (miR)‑19a‑5p and tet methylcytosine dioxygenase 2 (TET2) in OC and adjacent normal tissues. Furthermore, OC cells with GATA‑AS1 either knocked down or overexpressed were established. The Cell Counting Kit‑8 assay was used to evaluate cell proliferation and a Transwell assay was used to assess the migratory and invasive abilities of OC cells. A dual luciferase reporter gene assay was used to determine whether GATA6‑AS1 and miR‑19a‑5p, and miR‑19a‑5p and TET2, may interact with each other. The results demonstrated that GATA6‑AS1 expression level was decreased in OC tissues and cells compared with control groups. In addition, GATA6‑AS1 overexpression significantly inhibited the proliferation and migratory and invasive abilities of OC cells, whereas GATA6‑AS1 downregulation had the opposite effects. Furthermore, GATA6‑AS1 adsorbed miR‑19a‑5p to repress its expression and GTA6‑AS1 indirectly upregulated TET2 expression. Taken together, the findings from this study suggested that GATA6‑AS1 could inhibit the proliferation and migratory and invasive abilities of OC cells via regulation of the miR‑19a‑5p/TET2 axis.

View Figures

View References

1	Stewart C, Ralyea C and Lockwood S: Ovarian Cancer: An integrated review. Semin Oncol Nurs. 35:151–156. 2019. View Article : Google Scholar : PubMed/NCBI
2	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
3	Peng WX, Koirala P and Mo YY: LncRNA-mediated regulation of cell signaling in cancer. Oncogene. 36:5661–5667. 2017. View Article : Google Scholar : PubMed/NCBI
4	Li Z, Lu Q, Zhu D, Han Y, Zhou X and Ren T: Lnc-SNHG1 may promote the progression of non-small cell lung cancer by acting as a sponge of miR-497. Biochem Biophys Res Commun. 506:632–640. 2018. View Article : Google Scholar : PubMed/NCBI
5	Lei K, Liang X, Gao Y, Xu B, Xu Y, Li Y, Tao Y, Shi W and Liu J: Lnc-ATB contributes to gastric cancer growth through a miR-141-3p/TGFβ2 feedback loop. Biochem Biophys Res Commun. 484:514–521. 2017. View Article : Google Scholar : PubMed/NCBI
6	Ge YW, Gao HM and Wang ZM: Advances in study of genus curcuma. Zhongguo Zhong Yao Za Zhi. 32:2461–2467. 2007.(In Chinese). PubMed/NCBI
7	Li ZT, Zhang X, Wang DW, Xu J, Kou KJ, Wang ZW, Yong G, Liang DS and Sun XY: Overexpressed lncRNA GATA6-AS1 Inhibits LNM and EMT via FZD4 through the Wnt/β-catenin signaling pathway in GC. Mol Ther Nucleic Acids. 19:827–840. 2020. View Article : Google Scholar : PubMed/NCBI
8	Catela Ivkovic T, Voss G, Cornella H and Ceder Y: microRNAs as cancer therapeutics: A step closer to clinical application. Cancer Lett. 407:113–122. 2017. View Article : Google Scholar : PubMed/NCBI
9	Chen QQ, Shi JM, Ding Z, Xia Q, Zheng TS, Ren YB, Li M and Fan LH: Berberine induces apoptosis in non-small-cell lung cancer cells by upregulating miR-19a targeting tissue factor. Cancer Manag Res. 11:9005–9015. 2019. View Article : Google Scholar : PubMed/NCBI
10	Liu Y, Liu R, Yang F, Cheng R, Chen X, Cui S, Gu Y, Sun W, You C, Liu Z, et al: miR-19a promotes colorectal cancer proliferation and migration by targeting TIA1. Mol Cancer. 16:532017. View Article : Google Scholar : PubMed/NCBI
11	Wang Y, Zhao S, Zhu L, Zhang Q and Ren Y: miR-19a negatively regulated the expression of PTEN and promoted the growth of ovarian cancer cells. Gene. 670:166–173. 2018. View Article : Google Scholar : PubMed/NCBI
12	Zhang B, Liu Y and Zhang J: Silencing of miR-19a-3p enhances osteosarcoma cells chemosensitivity by elevating the expression of tumor suppressor PTEN. Oncol Lett. 17:414–421. 2019.PubMed/NCBI
13	Ren S and Xu Y: AC016405.3, a novel long noncoding RNA, acts as a tumor suppressor through modulation of TET2 by microRNA-19a-5p sponging in glioblastoma. Cancer Sci. 110:1621–1632. 2019. View Article : Google Scholar : PubMed/NCBI
14	Alven S and Aderibigbe BA: Nanoparticles formulations of artemisinin and derivatives as potential therapeutics for the treatment of cancer, leishmaniasis and malaria. Pharmaceutics. 12:7482020. View Article : Google Scholar : PubMed/NCBI
15	Sheng J, Wang L, Han Y, Chen W, Liu H, Zhang M, Deng L and Liu YN: Dual roles of protein as a template and a sulfur provider: A general approach to metal sulfides for efficient photothermal therapy of cancer. Small. Nov 17–2017.(Epub ahead of print). doi: 10.1002/smll.201702529.
16	Wang P, Wang J, Tan H, Weng S, Cheng L, Zhou Z and Wen S: Acid- and reduction-sensitive micelles for improving the drug delivery efficacy for pancreatic cancer therapy. Biomater Sci. 6:1262–1270. 2018. View Article : Google Scholar : PubMed/NCBI
17	Yang H, Liu Y, Bai F, Zhang JY, Ma SH, Liu J, Xu ZD, Zhu HG, Ling ZQ, Ye D, et al: Tumor development is associated with decrease of TET gene expression and 5-methylcytosine hydroxylation. Oncogene. 32:663–669. 2013. View Article : Google Scholar : PubMed/NCBI
18	Tucker DW, Getchell CR, McCarthy ET, Ohman AW, Sasamoto N, Xu S, Ko JY, Gupta M, Shafrir A, Medina JE, et al: Epigenetic reprogramming strategies to reverse global loss of 5-hydroxymethylcytosine, a prognostic factor for poor survival in high-grade serous ovarian cancer. Clin Cancer Res. 24:1389–1401. 2018. View Article : Google Scholar : PubMed/NCBI
19	Zhang LY, Li PL, Wang TZ and Zhang XC: Prognostic values of 5-hmC, 5-mC and TET2 in epithelial ovarian cancer. Arch Gynecol Obstet. 292:891–897. 2015. View Article : Google Scholar : PubMed/NCBI
20	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
21	Zou MF, Ling J, Wu QY and Zhang CX: Long non-coding RNA PVT1 functions as an oncogene in ovarian cancer via upregulating SOX2. Eur Rev Med Pharmacol Sci. 24:75712020.PubMed/NCBI
22	Martini P, Paracchini L, Caratti G, Mello-Grand M, Fruscio R, Beltrame L, Calura E, Sales G, Ravaggi A, Bignotti E, et al: lncRNAs as novel indicators of patients' prognosis in stage I epithelial ovarian cancer: A retrospective and multicentric study. Clin Cancer Res. 23:2356–2366. 2017. View Article : Google Scholar : PubMed/NCBI
23	Xie T, Wu D, Li S, Li X, Wang L, Lu Y, Song Q, Sun X and Wang X: microRNA-582 potentiates liver and lung metastasis of gastric carcinoma cells through the FOXO3-mediated PI3K/Akt/Snail pathway. Cancer Manag Res. 12:5201–5212. 2020. View Article : Google Scholar : PubMed/NCBI
24	Ni WJ and Leng XM: miRNA-dependent activation of mRNA Translation. Microrna. 5:83–86. 2016. View Article : Google Scholar : PubMed/NCBI
25	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
26	Xiang G and Cheng Y: miR-126-3p inhibits ovarian cancer proliferation and invasion via targeting PLXNB2. Reprod Biol. 18:218–224. 2018. View Article : Google Scholar : PubMed/NCBI
27	Xu ZH, Yao TZ and Liu W: miR-378a-3p sensitizes ovarian cancer cells to cisplatin through targeting MAPK1/GRB2. Biomed Pharmacother. 107:1410–1417. 2018. View Article : Google Scholar : PubMed/NCBI
28	Yang CB, Xiao SW, Cheng SM and Zhang C: LncRNA FAS-AS1 inhibits the progression of non-small cell lung cancer through regulating miR-19a-5p. Eur Rev Med Pharmacol Sci. 24:3775–3785. 2020.PubMed/NCBI
29	Liu GM, Lu TC, Sun ML, Ji X, Zhao YA, Jia WY and Luo YG: RP11-874J12.4 promotes oral squamous cell carcinoma tumorigenesis via the miR-19a-5p/EBF1 axis. J Oral Pathol Med. 49:645–654. 2020. View Article : Google Scholar : PubMed/NCBI
30	Sun HX, Yang ZF, Tang WG, Ke AW, Liu WR, Li Y, Gao C, Hu B, Fu PY, Yu MC, et al: MicroRNA-19a-3p regulates cell growth through modulation of the PIK3IP1-AKT pathway in hepatocellular carcinoma. J Cancer. 11:2476–2484. 2020. View Article : Google Scholar : PubMed/NCBI
31	Su YF, Zang YF, Wang YH and Ding YL: miR-19-3p induces tumor cell apoptosis via targeting FAS in rectal cancer cells. Technol Cancer Res Treat. 19:15330338209179782020. View Article : Google Scholar : PubMed/NCBI
32	Ko M, An J, Pastor WA, Koralov SB, Rajewsky K and Rao A: TET proteins and 5-methylcytosine oxidation in hematological cancers. Immunol Rev. 263:6–21. 2015. View Article : Google Scholar : PubMed/NCBI
33	Chiba S: Dysregulation of TET2 in hematologic malignancies. Int J Hematol. 105:17–22. 2017. View Article : Google Scholar : PubMed/NCBI
34	Ko M, Huang Y, Jankowska AM, Pape UJ, Tahiliani M, Bandukwala HS, An J, Lamperti ED, Koh KP, Ganetzky R, et al: Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2. Nature. 468:839–843. 2010. View Article : Google Scholar : PubMed/NCBI