Overexpression of microRNA‑96 is associated with poor prognosis and promotes proliferation, migration and invasion in cholangiocarcinoma cells via MTSS1

Yin,Xiaolan; Chai,Zongtao; Sun,Xiaoting; Chen,Jin; Wu,Xiufang; Yang,Liying; Zhou,Xiaobao; Liu,Feng

doi:10.3892/etm.2020.8502

Overexpression of microRNA‑96 is associated with poor prognosis and promotes proliferation, migration and invasion in cholangiocarcinoma cells via MTSS1

Authors:
- Xiaolan Yin
- Zongtao Chai
- Xiaoting Sun
- Jin Chen
- Xiufang Wu
- Liying Yang
- Xiaobao Zhou
- Feng Liu
View Affiliations

Affiliations: Department of Radiotherapy, Changhai Hospital (Hongkou District) Affiliated with Naval Medical University, Shanghai 200081, P.R. China, Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital Affiliated with Naval Medical University, Shanghai 200081, P.R. China, General Practitioners of Traditional Chinese Medicine, Wusong Street Community Health Service Center, Shanghai 200940, P.R. China
Published online on: February 7, 2020 https://doi.org/10.3892/etm.2020.8502
Pages: 2757-2765

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

MicroRNA‑96 (miR‑96) has been revealed serve an oncogenic role in various types of cancer. However, the role of miR‑96 in cholangiocarcinoma (CCA) development and progression is yet to be elucidated. Thus, the aim of the present study was to investigate the role of miR‑96 in CCA. The expression pattern of miR‑96 in CCA tissues and cell lines was evaluated using reverse transcription‑quantitative PCR analysis. Kaplan‑Meier curves and Cox regression analyses were conducted to investigate the prognostic significance of miR‑96 in CCA. Cell Counting Kit‑8 and Transwell assays were performed to identify the functions of miR‑96. The association between miR‑96 and metastasis suppressor‑1 (MTSS1) was verified using a dual‑luciferase assay. The results demonstrated that miR‑96 expression levels were increased in CCA tissues and cell lines compared with those in adjacent normal tissues and normal human intrahepatic biliary epithelial cell lines, respectively. High expression levels of miR‑96 were significantly associated with lymph node metastasis, differentiation and TNM stage. In addition, upregulated expression of miR‑96 was associated with a poorer prognosis and was predicted to be a prognostic factor in patients with CCA. Overexpression of miR‑96 in vitro promoted CCA cell proliferation, migration and invasion. Additionally, MTSS1 was identified as a direct target of miR‑96. The results of the present study indicated the clinical and biological importance of miR‑96 as an oncogene in CCA. miR‑96 may represent an independent prognostic biomarker and may promote CCA cell proliferation, migration and invasion by targeting MTSS1.

View Figures

View References

1	Rizvi S and Gores GJ: Pathogenesis, diagnosis, and management of cholangiocarcinoma. Gastroenterology. 145:1215–1229. 2013.PubMed/NCBI View Article : Google Scholar
2	Khan AS and Dageforde LA: Cholangiocarcinoma. Surg Clin North Am. 99:315–335. 2019.PubMed/NCBI View Article : Google Scholar
3	Khan SA, Tavolari S and Brandi G: Cholangiocarcinoma: Epidemiology and risk factors. Liver Int. 39 (Suppl 1):S19–S31. 2019.PubMed/NCBI View Article : Google Scholar
4	Razumilava N and Gores GJ: Cholangiocarcinoma. Lancet. 383:2168–2179. 2014.PubMed/NCBI View Article : Google Scholar
5	Patel T: Cholangiocarcinoma-controversies and challenges. Nat Rev Gastroenterol Hepatol. 8:189–200. 2011.PubMed/NCBI View Article : Google Scholar
6	Squadroni M, Tondulli L, Gatta G, Mosconi S, Beretta G and Labianca R: Cholangiocarcinoma. Crit Rev Oncol Hematol. 116:11–31. 2017.
7	Blechacz B: Cholangiocarcinoma: Current knowledge and new developments. Gut Liver. 11:13–26. 2017.PubMed/NCBI View Article : Google Scholar
8	Ebata T, Mizuno T, Yokoyama Y, Igami T, Sugawara G and Nagino M: Surgical resection for Bismuth type IV perihilar cholangiocarcinoma. Br J Surg. 105:829–838. 2018.PubMed/NCBI View Article : Google Scholar
9	Valencia-Sanchez MA, Liu J, Hannon GJ and Parker R: Control of translation and mRNA degradation by miRNAs and siRNAs. Genes Dev. 20:515–524. 2006.PubMed/NCBI View Article : Google Scholar
10	Wei R, Ye X, Zhao Y, Jia N, Liu T, Lian W, Wei H, Zhang G and Song L: MicroRNA-218 inhibits the cell proliferation and migration in clear cell renal cell carcinoma through targeting cancerous inhibitor of protein phosphatase 2A. Oncol Lett. 17:3211–3218. 2019.PubMed/NCBI View Article : Google Scholar
11	Yao R, Zheng H, Wu L and Cai P: miRNA-641 inhibits the proliferation, migration, and invasion and induces apoptosis of cervical cancer cells by directly targeting ZEB1. Onco Targets Ther. 11:8965–8976. 2018.PubMed/NCBI View Article : Google Scholar
12	Hrdlicka HC, Lee SK and Delany AM: MicroRNAs are critical regulators of osteoclast differentiation. Curr Mol Biol Rep. 5:65–74. 2019.PubMed/NCBI View Article : Google Scholar
13	Iwai N, Yasui K, Tomie A, Gen Y, Terasaki K, Kitaichi T, Soda T, Yamada N, Dohi O, Seko Y, et al: Oncogenic miR-96-5p inhibits apoptosis by targeting the caspase-9 gene in hepatocellular carcinoma. Int J Oncol. 53:237–245. 2018.PubMed/NCBI View Article : Google Scholar
14	Iseki Y, Shibutani M, Maeda K, Nagahara H, Fukuoka T, Matsutani S, Hirakawa K and Ohira M: MicroRNA-96 promotes tumor invasion in colorectal cancer via RECK. Anticancer Res. 38:2031–2035. 2018.PubMed/NCBI View Article : Google Scholar
15	Xie W, Sun F, Chen L and Cao X: miR-96 promotes breast cancer metastasis by suppressing MTSS1. Oncol Lett. 15:3464–3471. 2018.PubMed/NCBI View Article : Google Scholar
16	Collins AL, Wojcik S, Liu J, Frankel WL, Alder H, Yu L, Schmittgen TD, Croce CM and Bloomston M: A differential microRNA profile distinguishes cholangiocarcinoma from pancreatic adenocarcinoma. Ann Surg Oncol. 21:133–138. 2014.PubMed/NCBI View Article : Google Scholar
17	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.PubMed/NCBI View Article : Google Scholar
18	Shi W, Hasimu G, Wang Y, Li N, Chen M and Zhang H: MTSS1 is an independent prognostic biomarker for survival in intrahepatic cholangiocarcinoma patients. Am J Transl Res. 7:1974–1983. 2015.PubMed/NCBI
19	Wang F, Liu Y and Zhang H: Loss of MTSS1 expression is an independent prognostic factor for Hilar cholangiocarcinoma. Pathol Oncol Res. 19:815–820. 2013.PubMed/NCBI View Article : Google Scholar
20	Kirstein MM and Vogel A: Epidemiology and risk factors of cholangiocarcinoma. Visc Med. 32:395–400. 2016.PubMed/NCBI View Article : Google Scholar
21	Puik JR, Meijer LL, Le Large TY, Prado MM, Frampton AE, Kazemier G and Giovannetti E: miRNA profiling for diagnosis, prognosis and stratification of cancer treatment in cholangiocarcinoma. Pharmacogenomics. 18:1343–1358. 2017.PubMed/NCBI View Article : Google Scholar
22	Khan SA, Davidson BR, Goldin RD, Heaton N, Karani J, Pereira SP, Rosenberg WM, Tait P, Taylor-Robinson SD, Thillainayagam AV, et al: Guidelines for the diagnosis and treatment of cholangiocarcinoma: An update. Gut. 61:1657–1669. 2012.PubMed/NCBI View Article : Google Scholar
23	Yang ZQ, Wu CA and Cheng YX: Prognostic value of microRNA-133a expression and its clinicopathologic significance in Non-small cell lung cancer: A comprehensive study based on Meta-analysis and the TCGA database. Oncol Res Treat. 41:762–768. 2018.PubMed/NCBI View Article : Google Scholar
24	Wang JR, Liu B, Zhou L and Huang YX: MicroRNA-124-3p suppresses cell migration and invasion by targeting ITGA3 signaling in bladder cancer. Cancer Biomark. 24:159–172. 2019.PubMed/NCBI View Article : Google Scholar
25	Karimi N, Ali Hosseinpour Feizi M, Safaralizadeh R, Hashemzadeh S, Baradaran B, Shokouhi B and Teimourian S: Serum overexpression of miR-301a and miR-23a in patients with colorectal cancer. J Chin Med Assoc. 82:215–220. 2019.PubMed/NCBI View Article : Google Scholar
26	Sekar D, Mani P, Biruntha M, Sivagurunathan P and Karthigeyan M: Dissecting the functional role of microRNA 21 in osteosarcoma. Cancer Gene Ther. 26:179–182. 2019.PubMed/NCBI View Article : Google Scholar
27	Papadaki C, Stoupis G, Tsalikis L, Monastirioti A, Papadaki M, Maliotis N, Stratigos M, Mastrostamatis G, Mavroudis D and Agelaki S: Circulating miRNAs as a marker of metastatic disease and prognostic factor in metastatic breast cancer. Oncotarget. 10:966–981. 2019.PubMed/NCBI View Article : Google Scholar
28	Bertoli G, Cava C and Castiglioni I: MicroRNAs: New biomarkers for diagnosis, prognosis, therapy prediction and therapeutic tools for breast cancer. Theranostics. 5:1122–1143. 2015.PubMed/NCBI View Article : Google Scholar
29	Qin C, Huang RY and Wang ZX: Potential role of miR-100 in cancer diagnosis, prognosis, and therapy. Tumour Biol. 36:1403–1409. 2015.PubMed/NCBI View Article : Google Scholar
30	Sun D, Zhong J, Wei W, Chen X, Liu J and Hu Z: Identification of microRNA expression in sentinel lymph nodes from patients with breast cancer via RNA sequencing for diagnostic accuracy. J Gene Med. 21(e3075)2019.PubMed/NCBI View Article : Google Scholar
31	Fei X, Zhang J, Zhao Y, Sun M, Zhao H and Li S: MiR-96 promotes invasion and metastasis by targeting GPC3 in non-small cell lung cancer cells. Oncol Lett. 15:9081–9086. 2018.PubMed/NCBI View Article : Google Scholar
32	Ma X, Shi W, Peng L, Qin X and Hui Y: MiR-96 enhances cellular proliferation and tumorigenicity of human cervical carcinoma cells through PTPN9. Saudi J Biol Sci. 25:863–867. 2018.PubMed/NCBI View Article : Google Scholar
33	Li Z and Wang Y: miR-96 targets SOX6 and promotes proliferation, migration, and invasion of hepatocellular carcinoma. Biochem Cell Biol. 96:365–371. 2018.PubMed/NCBI View Article : Google Scholar
34	Yuan J, Dong R, Liu F, Zhan L, Liu Y, Wei J and Wang N: The miR-183/182/96 cluster functions as a potential carcinogenic factor and prognostic factor in kidney renal clear cell carcinoma. Exp Ther Med. 17:2457–2464. 2019.PubMed/NCBI View Article : Google Scholar
35	Sha HH, Wang DD, Chen D, Liu SW, Wang Z, Yan DL, Dong SC and Feng JF: MiR-138: A promising therapeutic target for cancer. Tumour Biol. 39(1010428317697575)2017.PubMed/NCBI View Article : Google Scholar
36	Zhou MH, Zhou HW, Liu M and Sun JZ: The role of miR-92b in cholangiocarcinoma patients. Int J Biol Markers. 33:293–300. 2018.PubMed/NCBI View Article : Google Scholar
37	Yang N, Zhou J, Li Q, Han F and Yu Z: miR-96 exerts carcinogenic effect by activating AKT/GSK-3β/β-catenin signaling pathway through targeting inhibition of FOXO1 in hepatocellular carcinoma. Cancer Cell Int. 19(38)2019.PubMed/NCBI View Article : Google Scholar
38	Liu K, Jiao XD, Hao JL, Qin BD, Wu Y, Chen W, Liu J, He X and Zang YS: MTSS1 inhibits metastatic potential and induces G2/M phase cell cycle arrest in gastric cancer. Onco Targets Ther. 12:5143–5152. 2019.PubMed/NCBI View Article : Google Scholar
39	Du P, Wang S, Tang X, An C, Yang Y and Jiang WG: Reduced expression of metastasis Suppressor-1 (MTSS1) accelerates progression of human bladder uroepithelium cell carcinoma. Anticancer Res. 37:4499–4505. 2017.PubMed/NCBI View Article : Google Scholar
40	Taylor MD, Bollt O, Iyer SC and Robertson GP: Metastasis suppressor 1 (MTSS1) expression is associated with reduced in-vivo metastasis and enhanced patient survival in lung adenocarcinoma. Clin Exp Metastasis. 35:15–23. 2018.PubMed/NCBI View Article : Google Scholar
41	Wang H, Zhao Y, Cao L, Zhang J, Wang Y and Xu M: Metastasis suppressor protein 1 regulated by PTEN suppresses invasion, migration, and EMT of gastric carcinoma by inactivating PI3K/AKT signaling. J Cell Biochem. 120:3447–3454. 2019.PubMed/NCBI View Article : Google Scholar