Linc‑OIP5 loss regulates migration and invasion in MDA‑MB‑231 breast cancer cells by inhibiting YAP1/JAG1 signaling

Zhu,Qing; Li,Yongsheng; Dong,Xiangmei; Yang,Yue; Wang,Hongyan; Guo,Sufen

doi:10.3892/ol.2019.11071

Linc‑OIP5 loss regulates migration and invasion in MDA‑MB‑231 breast cancer cells by inhibiting YAP1/JAG1 signaling

Authors:
- Qing Zhu
- Yongsheng Li
- Xiangmei Dong
- Yue Yang
- Hongyan Wang
- Sufen Guo
View Affiliations

Affiliations: Department of Pathology, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China, Department of Medical Imaging, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China, Department of Pathology, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China
Published online on: November 8, 2019 https://doi.org/10.3892/ol.2019.11071
Pages: 103-112
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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

Breast cancer is the most prevalent cancer among women, and diagnosis and treatment represent a substantial challenge due to the lack of adequate molecular targets. It has been shown that long noncoding RNAs (lncRNAs) serve pivotal roles in regulating gene expression in tumors. The roles of long intervening noncoding RNA (Linc)‑OIP5 has been demonstrated in different types of cancer; however, its function in breast cancer has not been determined. In the present study, expression of Linc‑OIP5, YAP1 (Hippo signaling component) and JAG1 (Notch signaling component) in breast cancer cells with different degrees of malignancy were determined. To assess whether Linc‑OIP5 regulated the malignant biological behaviors of MDA‑MB‑231 cells, its expression was knocked down using a specific small interfering RNA (siRNA), and cell proliferation was determined using a CCK‑8 assay, apoptosis was evaluated using an Annexin V‑FITC apoptosis detection kit, migration was assessed using a wound healing and transwell migration assays, and cell invasion examined using a transwell invasion assays. The effect of Linc‑OIP5 knockdown on YAP1 and JAG1 expression was quantified using reverse transcription‑quantitative PCR and immunoblotting. Cell proliferation, migration and invasion were reduced, while apoptosis was increased in MDA‑MB‑231 cells transfected with Linc‑OIP5‑specific siRNA. Mechanistic investigations showed that Linc‑OIP5 knockdown downregulated YAP1 and JAG1 expression. The results of the present study suggest that Linc‑OIP5 affects the malignant biological behaviors of MDA‑MB‑231 cells, at least partly through its effects on YAP1/JAG1 signaling. Whilst there are a number of mechanisms underlying the pathogenesis of breast cancer, the results of the present study highlight Linc‑OIP5 as a potential therapeutic target in breast cancer.

View Figures

View References

1	Lobba ARM, Carreira ACO, Cerqueira OLD, Fujita A, DeOcesano-Pereira C, Osorio CAB, Soares FA, Rameshwar P and Sogayar MC: High CD90 (THY-1) expression positively correlates with cell transformation and worse prognosis in basal-like breast cancer tumors. PLoS One. 13:e01992542018. View Article : Google Scholar : PubMed/NCBI
2	Fan S, Fan C, Liu N, Huang K, Fang X and Wang K: Downregulation of the long non-coding RNA ZFAS1 is associated with cell proliferation, migration and invasion in breast cancer. Mol Med Rep. 17:6405–6412. 2018.PubMed/NCBI
3	Zhao W, Geng D, Li S, Chen Z and Sun M: LncRNA HOTAIR influences cell growth, migration, invasion, and apoptosis via the miR-20a-5p/HMGA2 axis in breast cancer. Cancer Med. 7:842–855. 2018. View Article : Google Scholar : PubMed/NCBI
4	Wang P, Wang F, Wang L and Pan JH: Proprotein convertase subtilisin/kexin type 6 activates the extracellular signal-regulated kinase 1/2 and Wnt family member 3A pathways and promotes in vitro proliferation, migration and invasion of breast cancer MDA-MB-231 cells. Oncol Lett. 16:145–150. 2018.PubMed/NCBI
5	Liang Y, Chen H, Ji L, Du J, Xie X, Li X and Lou Y: Talin2 regulates breast cancer cell migration and invasion by apoptosis. Oncol Lett. 16:285–293. 2018.PubMed/NCBI
6	Wen Y, Ji Y, Zhang Y, Jiang B, Tang C, Wang Q, Chen X, Jia L, Gu W and Xu X: Knockdown of Yes-associated protein induces the apoptosis while inhibits the proliferation of human periodontal ligament stem cells through crosstalk between Erk and Bcl-2 signaling pathways. Int J Med Sci. 14:1231–1240. 2017. View Article : Google Scholar : PubMed/NCBI
7	Jiang N, Ke B, Hjortjensen K, Iglesiasgato D, Wang Z, Chang PC, Zhao Y, Niu XD, Wu T, Peng B, et al: YAP1 regulates prostate cancer stem cell-like characteristics to promote castration resistant growth. Oncotarget. 8:115054–115067. 2017. View Article : Google Scholar : PubMed/NCBI
8	Xu Y, Lin X, Xu J, Jing H, Qin Y and Li Y: SULT1E1 inhibits cell proliferation and invasion by activating PPARγ in breast cancer. J Cancer. 9:1078–1087. 2018. View Article : Google Scholar : PubMed/NCBI
9	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
10	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
11	Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:e359–e386. 2015. View Article : Google Scholar : PubMed/NCBI
12	Deng J, Deng H, Liu C, Liang Y and Wang S: Long non-coding RNA OIP5-AS1 functions as an oncogene in lung adenocarcinoma through targeting miR-448/Bcl-2. Biomed Pharmacother. 98:102–110. 2018. View Article : Google Scholar : PubMed/NCBI
13	Mendell JT: Targeting a long noncoding RNA in breast cancer. N Engl J Med. 374:2287–2289. 2016. View Article : Google Scholar : PubMed/NCBI
14	Arun G, Diermeier S, Akerman M, Chang KC, Wilkinson JE, Hearn S, Kim Y, MacLeod AR, Krainer AR, Norton L, et al: Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss. Genes Dev. 30:34–51. 2016. View Article : Google Scholar : PubMed/NCBI
15	Bergmann JH and Spector DL: Long non-coding RNAs: Modulators of nuclear structure and function. Curr Opin Cell Biol. 26:10–18. 2014. View Article : Google Scholar : PubMed/NCBI
16	Rinn JL and Chang HY: Genome regulation by long noncoding RNAs. Ann Rev Biochem. 81:145–166. 2012. View Article : Google Scholar : PubMed/NCBI
17	Meseure D, Drak Alsibai K, Nicolas A, Bieche I and Morillon A: Long noncoding RNAs as new architects in cancer epigenetics, prognostic biomarkers, and potential therapeutic targets. Biomed Res Int. 2015:3202142015. View Article : Google Scholar : PubMed/NCBI
18	Pandey GK and Kanduri C: Long noncoding RNAs and neuroblastoma. Oncotarget. 6:18265–18275. 2015. View Article : Google Scholar : PubMed/NCBI
19	Yang N, Chen J, Zhang H, Wang X, Yao H, Peng Y and Zhang WG: LncRNA OIP5-AS1 loss-induced microRNA-410 accumulation regulates cell proliferation and apoptosis by targeting KLF10 via activating PTEN/PI3K/AKT pathway in multiple myeloma. Cell Death Dis. 8:e29752017. View Article : Google Scholar : PubMed/NCBI
20	Wu N, Nguyen Q, Wan Y, Zhou T, Venter J, Frampton GA, DeMorrow S, Pan D, Meng F, Glaser S, et al: The Hippo signaling functions through the Notch signaling to regulate intrahepatic bile duct development in mammals. Lab Invest. 97:843–853. 2017. View Article : Google Scholar : PubMed/NCBI
21	Gonzalez-King H, García NA, Ontoria-Oviedo I, Ciria M, Montero JA and Sepúlveda P: Hypoxia Inducible Factor-1α potentiates Jagged1-mediated angiogenesis by mesenchymal stem cell-derived exosomes. Stem Cells. 35:1747–1759. 2017. View Article : Google Scholar : PubMed/NCBI
22	Sheldon H, Heikamp E, Turley H, Dragovic R, Thomas P, Oon CE, Leek R, Edelmann M, Kessler B, Sainson RC, et al: New mechanism for Notch signaling to endothelium at a distance by Delta-like 4 incorporation into exosomes. Blood. 116:2385–2394. 2010. View Article : Google Scholar : PubMed/NCBI
23	Pan D: Hippo signaling in organ size control. Genes Dev. 21:886–897. 2007. View Article : Google Scholar : PubMed/NCBI
24	Pan D: The hippo signaling pathway in development and cancer. Dev Cell. 19:491–505. 2010. View Article : Google Scholar : PubMed/NCBI
25	Yimlamai D, Christodoulou C, Galli GG, Yanger K, Pepe-Mooney B, Gurung B, Shrestha K, Cahan P, Stanger BZ and Camargo FD: Hippo pathway activity influences liver cell fate. Cell. 157:1324–1338. 2014. View Article : Google Scholar : PubMed/NCBI
26	Ramos A and Camargo FD: The Hippo signaling pathway and stem cell biology. Trends Cell Biol. 22:339–346. 2012. View Article : Google Scholar : PubMed/NCBI
27	Mammoto A, Muyleart M, Kadlec A, Gutterman D and Mammoto T: YAP1-TEAD1 signaling controls angiogenesis and mitochondrial biogenesis through PGC1α. Microvas Res. 119:73–83. 2018. View Article : Google Scholar
28	Oon CE, Bridges E, Sheldon H, Sainson RCA, Jubb A, Turley H, Leek R, Buffa F, Harris AL and Li JL: Role of Delta-like 4 in Jagged1-induced tumour angiogenesis and tumour growth. Oncotarget. 8:40115–40131. 2017. View Article : Google Scholar : PubMed/NCBI
29	Benedito R, Roca C, Sörensen I, Adams S, Gossler A, Fruttiger M and Adams RH: The notch ligands Dll4 and Jagged1 have opposing effects on angiogenesis. Cell. 137:1124–1135. 2009. View Article : Google Scholar : PubMed/NCBI
30	Aspalter IM, Gordon E, Dubrac A, Ragab A, Narloch J, Vizán P, Geudens I, Collins RT, Franco CA, Abrahams CL, et al: Alk1 and Alk5 inhibition by Nrp1 controls vascular sprouting downstream of Notch. Nat Comm. 17:72642015. View Article : Google Scholar
31	Lin C and Xu X: YAP1-TEAD1-Glut1 axis dictates the oncogenic phenotypes of breast cancer cells by modulating glycolysis. Biomed Pharmacother. 95:789–794. 2017. View Article : Google Scholar : PubMed/NCBI
32	Wang T, Mao B, Cheng C, Zou Z, Gao J, Yang Y, Lei T, Qi X, Yuan Z, Xu W and Lu Z: YAP promotes breast cancer metastasis by repressing growth differentiation factor-15. Biochim Biophys Acta Mol Basis Dis. 1864:1744–1753. 2018. View Article : Google Scholar : PubMed/NCBI
33	Wu Q, Li J and Sun S, Chen X, Zhang H, Li B and Sun S: YAP/TAZ-mediated activation of serine metabolism and methylation regulation is critical for LKB1-deficient breast cancer progression. Biosci Rep. 37(pii): BSR201710722017. View Article : Google Scholar : PubMed/NCBI
34	Hou L, Chen L and Fang L: Scutellarin inhibits proliferation, invasion, and tumorigenicity in human breast cancer cells by regulating HIPPO-YAP signaling pathway. Med Sci Monit. 23:5130–5138. 2017. View Article : Google Scholar : PubMed/NCBI
35	Selcuklu SD, Donoghue MT, Kerin MJ and Spillane C: Regulatory interplay between miR-21, JAG1 and 17beta-estradiol (E2) in breast cancer cells. Biochem Biophys Res Commun. 423:234–239. 2012. View Article : Google Scholar : PubMed/NCBI
36	Dickson BC, Mulligan AM, Zhang H, Lockwood G, O'Malley FP, Egan SE and Reedijk M: High-level JAG1 mRNA and protein predict poor outcome in breast cancer. Mod Pathol. 20:685–693. 2007. View Article : Google Scholar : PubMed/NCBI
37	Reedijk M, Pinnaduwage D, Dickson BC, Mulligan AM, Zhang H, Bull SB, O'Malley FP, Egan SE and Andrulis IL: JAG1 expression is associated with a basal phenotype and recurrence in lymph node-negative breast cancer. Breast Cancer Res Treat. 111:439–448. 2008. View Article : Google Scholar : PubMed/NCBI
38	Slemmons KK, Crose LES, Riedel S, Sushnitha M, Belyea B and Linardic CM: A novel Notch-YAP circuit drives stemness and tumorigenesis in embryonal rhabdomyosarcoma. Mol Cancer Res. 15:1777–1791. 2017. View Article : Google Scholar : PubMed/NCBI
39	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
40	Zeng H, Wang J, Chen T, Zhang K, Chen J, Wang L, Li H, Tuluhong D, Li J and Wang S: Downregulation of long non-coding RNA Opa interacting protein 5-antisense RNA 1 inhibits breast cancer progression by targeting sex-determining region Y-box 2 by microRNA-129-5p upregulation. Cancer Sci. 110:289–302. 2019.PubMed/NCBI
41	Yilmaz M and Christofori G: EMT, the cytoskeleton, and cancer cell invasion. Cancer Metastasis Rev. 28:15–33. 2009. View Article : Google Scholar : PubMed/NCBI
42	Klymkowsky MW and Savagner P: Epithelial-mesenchymal transition: A cancer researcher's conceptual friend and foe. Am J Pathol. 174:1588–1593. 2009. View Article : Google Scholar : PubMed/NCBI
43	Ansieau S, Courtois-Cox S, Morel AP and Puisieux A: Failsafe program escape and EMT: A deleterious partnership. Semin Cancer Biol. 21:392–396. 2011.PubMed/NCBI