Long non‑coding RNA <em>ASAP1‑IT1</em> suppresses ovarian cancer progression by regulating Hippo/YAP signaling

Wang,Ke; Hu,Yu-Bo; Zhao,Ye; Ye,Cong

doi:10.3892/ijmm.2021.4877

Long non‑coding RNA ASAP1‑IT1 suppresses ovarian cancer progression by regulating Hippo/YAP signaling

Authors:
- Ke Wang
- Yu-Bo Hu
- Ye Zhao
- Cong Ye
View Affiliations

Affiliations: Department of Gynecology and Obstetrics, The China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130000, P.R. China, Department of Anesthesiology, The China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130000, P.R. China, Department of Dermatology, The China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130000, P.R. China
Published online on: February 8, 2021 https://doi.org/10.3892/ijmm.2021.4877
Article Number: 44

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

Long non‑coding RNAs (lncRNAs) are a class of non‑protein coding transcripts that are involved in the regulation of gene expression in mammalian cells. Transcriptional co‑activator Yes associated protein 1 (YAP1) plays a key role in the progression of ovarian cancer. However, the regulation of Hippo/YAP signaling in ovarian cancer remains elusive. In the present study, the expression levels of lncRNA ASAP1‑IT1 were investigated. The analysis indicated that lncRNA ASAP1‑IT1 expression was downregulated in ovarian tumor samples and ovarian cancer cells. The overexpression of ASAP1‑IT1 inhibited ovarian cancer cell proliferation and induced cell apoptosis. Bioinformatics analysis predicted that miR‑2278, a previously reported upregulated miRNA in ovarian tumors, may bind to ASAP1‑IT1. Dual luciferase assay confirmed the direct regulatory association between ASAP1‑IT1 and miR‑2278. In addition, the data demonstrated that large tumor suppressor 2 (LATS2) was a target gene of miR‑2278, whose expression was upregulated by ASAP1‑IT1 in ovarian cancer cells. By regulating the expression of LATS2, ASAP1‑IT1 induced the downregulation of YAP1 expression in ovarian cancer cells. Moreover, the silencing of LATS2 attenuated the inhibition of cell proliferation and the apoptosis induced by ASAP1‑IT1 overexpression in ovarian cancer cells. The association among the expression levels of ASAP1‑IT1, miR‑2278 and LATS2 was observed in specimens obtained from patients with ovarian cancer. Taken together, the data presented herein demonstrate that ASAP1‑IT1 functions as a potential tumor suppressor lncRNA by upregulating LATS2 expression in ovarian cancer.

View Figures

View References

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	Prat J: New insights into ovarian cancer pathology. Ann Oncol. 23(Suppl 10): x111–x117. 2012. View Article : Google Scholar : PubMed/NCBI
3	Lheureux S, Gourley C, Vergote I and Oza AM: Epithelial ovarian cancer. Lancet. 393:1240–1253. 2019. View Article : Google Scholar : PubMed/NCBI
4	Castro-Oropeza R, Melendez-Zajgla J, Maldonado V and Vazquez-Santillan K: The emerging role of lncRNAs in the regulation of cancer stem cells. Cell Oncol (Dordr). 41:585–603. 2018. View Article : Google Scholar
5	Salmena L, Poliseno L, Tay Y, Kats L and Pandolfi PP: A ceRNA hypothesis: The rosetta stone of a hidden RNA language? Cell. 146:353–358. 2011. View Article : Google Scholar : PubMed/NCBI
6	Zhang X, Hamblin MH and Yin KJ: The long noncoding RNA malat1: Its physiological and pathophysiological functions. RNA Biol. 14:1705–1714. 2017. View Article : Google Scholar : PubMed/NCBI
7	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
8	Mitra R, Chen X, Greenawalt EJ, Maulik U, Jiang W, Zhao Z and Eischen CM: Decoding critical long non-coding RNA in ovarian cancer epithelial-to-mesenchymal transition. Nat Commun. 8:16042017. View Article : Google Scholar : PubMed/NCBI
9	Wu DD, Chen X, Sun KX, Wang LL, Chen S and Zhao Y: Role of the lncRNA ABHD11-AS1 in the tumorigenesis and progression of epithelial ovarian cancer through targeted regulation of RhoC. Mol Cancer. 16:1382017. View Article : Google Scholar :
10	Yang L, Xue Y, Liu J, Zhuang J, Shen L, Shen B, Yan J and Guo H: Long noncoding RNA ASAP1-IT1 promotes cancer stemness and predicts a poor prognosis in patients with bladder cancer. Neoplasma. 64:847–855. 2017. View Article : Google Scholar : PubMed/NCBI
11	Fu Y, Biglia N, Wang Z, Shen Y, Risch HA, Lu L, Canuto EM, Jia W, Katsaros D and Yu H: Long non-coding RNAs, ASAP1-IT1, FAM215A, and LINC00472, in epithelial ovarian cancer. Gynecol Oncol. 143:642–649. 2016. View Article : Google Scholar : PubMed/NCBI
12	Yu FX, Zhao B, Panupinthu N, Jewell JL, Lian I, Wang LH, Zhao J, Yuan H, Tumaneng K, Li H, et al: Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling. Cell. 150:780–791. 2012. View Article : Google Scholar : PubMed/NCBI
13	Overholtzer M, Zhang J, Smolen GA, Muir B, Li W, Sgroi DC, Deng CX, Brugge JS and Haber DA: Transforming properties of YAP, a candidate oncogene on the chromosome 11q22 amplicon. Proc Natl Acad Sci USA. 103:12405–12410. 2006. View Article : Google Scholar : PubMed/NCBI
14	Pan Y, Tong JHM, Lung RWM, Kang W, Kwan JSH, Chak WP, Tin KY, Chung LY, Wu F, Ng SSM, et al: RASAL2 promotes tumor progression through LATS2/YAP1 axis of hippo signaling pathway in colorectal cancer. Mol Cancer. 17:1022018. View Article : Google Scholar : PubMed/NCBI
15	Dong L, Lin F, Wu W, Liu Y and Huang W: Verteporfin inhibits YAP-induced bladder cancer cell growth and invasion via Hippo signaling pathway. Int J Med Sci. 15:645–652. 2018. View Article : Google Scholar : PubMed/NCBI
16	Yu S, Cai X, Wu C, Wu L, Wang Y, Liu Y, Yu Z, Qin S, Ma F, Thiery JP and Chen L: Adhesion glycoprotein CD44 functions as an upstream regulator of a network connecting ERK, AKT and Hippo-YAP pathways in cancer progression. Oncotarget. 6:2951–2965. 2015. View Article : Google Scholar : PubMed/NCBI
17	Yan H, Li H, Silva MA, Guan Y, Yang L, Zhu L, Zhang Z, Li G and Ren C: LncRNA FLVCR1-AS1 mediates miR-513/YAP1 signaling to promote cell progression, migration, invasion and EMT process in ovarian cancer. J Exp Clin Cancer Res. 38:3562019. View Article : Google Scholar : PubMed/NCBI
18	Yan H, Li H, Li P, Li X, Lin J, Zhu L, Silva MA, Wang X, Wang P and Zhang Z: Long noncoding RNA MLK7-AS1 promotes ovarian cancer cells progression by modulating miR-375/YAP1 axis. J Exp Clin Cancer Res. 37:2372018. View Article : Google Scholar : PubMed/NCBI
19	Guo C, Wang X and Liang L: LATS2-mediated YAP1 phosphorylation is involved in HCC tumorigenesis. Int J Clin Exp Pathol. 8:1690–1697. 2015.PubMed/NCBI
20	Guo Y, Cui J, Ji Z, Cheng C, Zhang K, Zhang C, Chu M, Zhao Q, Yu Z, Zhang Y, et al: miR-302/367/LATS2/YAP pathway is essential for prostate tumor-propagating cells and promotes the development of castration resistance. Oncogene. 36:6336–6347. 2017. View Article : Google Scholar : PubMed/NCBI
21	Xia Y and Gao Y: MicroRNA-181b promotes ovarian cancer cell growth and invasion by targeting LATS2. Biochem Biophys Res Commun. 447:446–451. 2014. View Article : Google Scholar : PubMed/NCBI
22	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
23	Chen Y and Wang X: miRDB: An online database for prediction of functional microRNA targets. Nucleic Acids Res. 48(D1): D127–D131. 2020. View Article : Google Scholar :
24	Agarwal V, Bell GW, Nam JW and Bartel DP: Predicting effective microRNA target sites in mammalian mRNAs. Elife. 4:e050052015. View Article : Google Scholar :
25	Cordenonsi M, Zanconato F, Azzolin L, Forcato M, Rosato A, Frasson C, Inui M, Montagner M, Parenti AR, Poletti A, et al: The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells. Cell. 147:759–772. 2011. View Article : Google Scholar : PubMed/NCBI
26	Melhem A, Yamada SD, Fleming GF, Delgado B, Brickley DR, Wu W, Kocherginsky M and Conzen SD: Administration of glucocorticoids to ovarian cancer patients is associated with expression of the anti-apoptotic genes SGK1 and MKP1/DUSP1 in ovarian tissues. Clin Cancer Res. 15:3196–3204. 2009. View Article : Google Scholar : PubMed/NCBI
27	Li R, Wang Y, Xu Y, He X and Li Y: Silencing the long noncoding RNA, TINCR, a molecular sponge of miR335, inhibits the malignant phenotype of epithelial ovarian cancer via FGF2 suppression. Int J Oncol. 55:1110–1124. 2019.PubMed/NCBI
28	Llaurado M, Abal M, Castellvi J, Cabrera S, Gil-Moreno A, Pérez-Benavente A, Colás E, Doll A, Dolcet X, Matias-Guiu X, et al: ETV5 transcription factor is overexpressed in ovarian cancer and regulates cell adhesion in ovarian cancer cells. Int J Cancer. 130:1532–1543. 2012. View Article : Google Scholar
29	Todeschini P, Salviato E, Paracchini L, Ferracin M, Petrillo M, Zanotti L, Tognon G, Gambino A, Calura E, Caratti G, et al: Circulating miRNA landscape identifies miR-1246 as promising diagnostic biomarker in high-grade serous ovarian carcinoma: A validation across two independent cohorts. Cancer Lett. 388:320–327. 2017. View Article : Google Scholar
30	Li J, Yang C, Li Y, Chen A, Li L and You Z: LncRNA GAS5 suppresses ovarian cancer by inducing inflammasome formation. Biosci Rep. 38:BSR201711502018. View Article : Google Scholar :
31	An J, Lv W and Zhang Y: LncRNA NEAT1 contributes to paclitaxel resistance of ovarian cancer cells by regulating ZEB1 expression via miR-194. Onco Targets Ther. 10:5377–5390. 2017. View Article : Google Scholar : PubMed/NCBI
32	Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI
33	Muller T, Stein U, Poletti A, Garzia L, Rothley M, Plaumann D, Thiele W, Bauer M, Galasso A, Schlag P, et al: ASAP1 promotes tumor cell motility and invasiveness, stimulates metastasis formation in vivo, and correlates with poor survival in colorectal cancer patients. Oncogene. 29:2393–2403. 2010. View Article : Google Scholar : PubMed/NCBI
34	Zhang L, Shi SB, Zhu Y, Qian TT and Wang HL: Long non-coding RNA ASAP1-IT1 promotes cell proliferation, invasion and metastasis through the PTEN/AKT signaling axis in non-small cell lung cancer. Eur Rev Med Pharmacol Sci. 22:142–149. 2018.PubMed/NCBI
35	Guo L, Zhou Y, Chen Y, Sun H, Wang Y and Qu Y: LncRNA ASAP1-IT1 positively modulates the development of cholangiocarcinoma via hedgehog signaling pathway. Biomed Pharmacother. 103:167–173. 2018. View Article : Google Scholar : PubMed/NCBI
36	Wang Y, Justilien V, Brennan KI, Jamieson L, Murray NR and Fields AP: PKCiota regulates nuclear YAP1 localization and ovarian cancer tumorigenesis. Oncogene. 36:534–545. 2017. View Article : Google Scholar
37	He C, Lv X, Huang C, Hua G, Ma B, Chen X, Angeletti PC, Dong J, Zhou J, Wang Z, et al: YAP1-LATS2 feedback loop dictates senescent or malignant cell fate to maintain tissue homeostasis. EMBO Rep. 20:e449482019. View Article : Google Scholar : PubMed/NCBI