Lentiviral-Mediated Overexpression of MicroRNA-141 Promotes Cell Proliferation and Inhibits Apoptosis in Human Esophageal Squamous Cell Carcinoma

Author(s): Jun-He Zhang , Hai-Bin Xia* .

Journal Name: Recent Patents on Anti-Cancer Drug Discovery

Volume 14 , Issue 2 , 2019

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Abstract:

Background: Esophageal Carcinoma (EC) is the eighth most common cancer worldwide. Numerous studies have highlighted a vital role of microRNAs (miRNAs) in the development of EC. However, the mechanism of microRNA (miRNA)-141 in Esophageal Squamous Cell Carcinoma (ESCC) remains unknown.

Objective: In this study, we explored the effects of miRNA-141 on EC cell proliferation, apoptosis, xenograft tumour growth and their possible mechanisms.

Methods: A lentivirus-vector-expressing miRNA-141 was constructed, and a TE-1 cell line of ESCC with a stable expression of miRNA-141 was transfected and screened. The miRNA-141 expression level was detected using qRT-PCR. Effects of miRNA-141 overexpression on cell proliferation and apoptosis were detected using MTT and flow cytometry, respectively. Using a dual-luciferase reporter assay, a direct interaction between miRNA-141 and the 3'-Untranslated Region (UTR) of YAP1 and SOX17 was confirmed. Tumour xenograft experiment in nude mice was used to detect the tumour growth, and the effects of miRNA-141 overexpression on YAP1 and SOX17 were analysed using Western blot.

Results: We found that miRNA-141 was highly expressed in TE-1 cells, and miRNA-141 overexpression promoted cell proliferation and inhibited apoptosis. Moreover, the miRNA-141 group showed significantly increased tumour growth ability, luciferase activities and expression levels of YAP1 and SOX17 in the miRNA-141group were significantly down-regulated.

Conclusion: miRNA-141 promotes cell proliferation and inhibits apoptosis in ESCC by downregulating the expression level of YAP1 and SOX17, indicating that miRNA-141 may be a potential molecular target for the treatment of ESCC.

Keywords: Apoptosis, esophageal squamous cell carcinoma, gene therapy, lentiviral vector, miRNA-141, proliferation.

[1]
Domper Arnal MJ, Ferrández Arenas Á, Lanas Arbeloa Á. Esophageal cancer: Risk factors, screening and endoscopic treatment in Western and Eastern countries. World J Gastroenterol 2015; 21(26): 7933-43.
[2]
Zhang L, Hu S, Korteweg C, Chen Z, Qiu Y, Su M, et al. Expression of immunoglobulin G in esophageal squamous cell carcinomas and its association with tumor grade and Ki67. Hum Pathol 2012; 43(3): 423-34.
[3]
Kandioler D, Schoppmann SF, Zwrtek R, Kappel S, Wolf B, Mittlböck M, et al. The biomarker TP53 divides patients with neoadjuvantly treated esophageal cancer into 2 subgroups with markedly different outcomes. A p53 Research Group study. J Thorac Cardiovasc Surg 2014; 148(5): 2280-6.
[4]
Sarkar J, Dominguez E, Li G, Kusewitt DF, Johnson DG. Modeling gene-environment interactions in oral cavity and esophageal cancers demonstrates a role for the p53 R72P polymorphism in modulating susceptibility. Mol Carcinog 2014; 53(8): 648-58.
[5]
Murata A, Baba Y, Watanabe M, Shigaki H, Miyake K, Karashima R, et al. p53 Immunohistochemical expression and patient prognosis in esophageal squamous cell carcinoma. Med Oncol 2013; 30(4): 728-35.
[6]
Gomes TS, Noguti J, Forones NM, Lima FO, Dobo C, Fernandes Junior J.A., et al. Correlation analysis of c-myc, p21(WAF/CIP1), p53, CERBB-2 and COX-2 proteins in esophageal squamous cell carcinoma. Pathol Res Pract 2013; 209(1): 6-9.
[7]
Li H, Xiao W, Ma J, Zhang Y, Li R, Ye J, et al. Dual high expression of STAT3 and cyclinD1 is associated with poor prognosis after curative resection of esophageal squamous cell carcinoma. Int J Clin Exp Pathol 2014; 7(11): 7989-98.
[8]
Mohr AM, Mott JL. Overview of microRNA biology. Semin Liver Dis 2015; 35(1): 3-11.
[9]
Li J, Tan S, Kooger R, Zhang C, Zhang Y. MicroRNAs as novel biological targets for detection and regulation. Chem Soc Rev 2014; 43(2): 506-17.
[10]
Ribeiro AO, Schoof CR, Izzotti A, Pereira LV, Vasques LR. MicroRNAs: Modulators of cell identity, and their applications in tissue engineering. MicroRNA 2014; 3(1): 45-53.
[11]
Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P, et al. MicroRNA signatures in human ovarian cancer. Cancer Res 2007; 67(18): 8699-1707.
[12]
Liu Y, Ding Y, Huang J, Wang S, Ni W, Guan J, et al. MiR-141 suppresses the migration and invasion of HCC cells by targeting Tiam1. PLoS One 2014; 9(2)e88393
[13]
Zhang JH, Du AL, Wang L, Wang XY, Gao JH, Wang TY. Episomal lentiviral vector-mediated miR-145 overexpression inhibits proliferation and induces apoptosis of human esophageal carcinomas cells. Recent Patents Anticancer Drug Discov 2016; 11(4): 453-60.
[14]
Fan JD, Jiang LX, Zhou ZW. Recombinant lentiviral vector preparation. US2015056696 (2015).
[15]
Imanaka Y, Tsuchiya S, Sato F, Shimada Y, Shimizu K, Tsujimoto G. MicroRNA-141 confers resistance to cisplatin-induced apoptosis by targeting YAP1 in human esophageal squamous cell carcinoma. J Hum Genet 2011; 56(4): 270-6.
[16]
Jia Y, Yang Y, Zhan Q, Brock MV, Zheng X, Yu Y, et al. Inhibition of SOX17 by microRNA 141 and methylation activates the WNT signaling pathway in esophageal cancer. J Mol Diagn 2012; 14(6): 577-85.
[17]
Kato H, Nakajima M. Treatments for esophageal cancer: A review. Gen Thorac Cardiovasc Surg 2013; 61(6): 330-5.
[18]
Croce CM. MicroRNA signatures in human ovarian cancer. US2015024963 (2015).
[19]
Wang X. Rational design of microRNA-siRNA chimeras for multifunctional target suppression. US2015099793 (2015).
[20]
Wu J, Jiang C. MicroRNA molecular marker for diagnosing glioma and application of microRNA molecular marker. CN104313171 (2015).
[21]
Simonson B, Das S. MicroRNA therapeutics: The next magic bullet? Mini Rev Med Chem 2015; 15(6): 467-74.
[22]
Igaz P, Igaz I, Nagy Z, Nyírő G, Szabó PM, Falus A, et al. MicroRNAs in adrenal tumors: Relevance for pathogenesis, diagnosis, and therapy. Cell Mol Life Sci 2015; 72(3): 417-28.
[23]
Fischer SE. RNA interference and microRNA-mediated silencing Curr Protoc Mol Biol 2015; 112: (26.1).1-5.
[24]
Bendoraite A, Knouf EC, Garg KS, Parkin RK, Kroh EM, O’Briant KC, et al. Regulation of miR-200 family microRNAs and ZEB transcription factors in ovarian cancer: Evidence supporting a mesothelial-to-epithelial transition. Gynecol Oncol 2010; 116(1): 117-25.
[25]
Mak CS, Yung MM, Hui LM, Leung LL, Liang R, Chen K, et al. MicroRNA-141 enhances anoikis resistance in metastatic progression of ovarian cancer through targeting KLF12/Sp1/survivin axis. Mol Cancer 2017; 16(1): 11.
[26]
Zhang L, Deng T, Li X, Liu H, Zhou H, Ma J, et al. MicroRNA-141 is involved in a nasopharyngeal carcinoma-related genes network. Carcinogenesis 2010; 31(4): 559-66.
[27]
Wu PP, Zhu HY, Sun XF, Chen LX, Zhou Q, Chen J. MicroRNA-141 regulates the tumor suppressor DLC1 in colorectal cancer. Neoplasma 2015; 62(5): 705-12.
[28]
Osipov ID, Zaporozhchenko IA, Bondar AA, Zaripov MM, Voytsitskiy VE, Vlassov VV, et al. Cell-Free miRNA-141 and miRNA-205 as prostate cancer biomarkers. Adv Exp Med Biol 2016; 924: 9-12.
[29]
Zhang X, Li P, Rong M, He R, Hou X, Xie Y, et al. MicroRNA-141 is a biomarker for progression of squamous cell carcinoma and adenocarcinoma of the lung: Clinical analysis of 125 patients. Tohoku J Exp Med 2015; 235(3): 161-9.
[30]
Berkers J, Govaere O, Wolter P, Beuselinck B, Schöffski P, van Kempen LC, et al. A possible role for microRNA-141 down-regulation in sunitinib resistant metastatic clear cell renal cell carcinoma through induction of epithelial-to-mesenchymal transition and hypoxia resistance. J Urol 2013; 189(5): 1930-8.
[31]
Xiao B, Zou QM, Zuo QF, Gong L. Application of micro RNA-141 as inhibitor. CN104491880 (2015).
[32]
Kodaka M, Hata Y. The mammalian hippo pathway: Regulation and function of YAP1 and TAZ. Cell Mol Life Sci 2015; 72(2): 285-306.
[33]
Yu SJ, Hu JY, Kuang XY, Luo JM, Hou YF, Di GH, et al. MicroRNA-200a promotes anoikis resistance and metastasis by targeting YAP1 in human breast cancer. Clin Cancer Res 2013; 19(6): 1389-99.
[34]
Yu SJ, Yang L, Hong Q, Kuang XY, Di GH, Shao ZM. MicroRNA-200a confers chemoresistance by antagonizing TP53INP1 and YAP1 in human breast cancer. BMC Cancer 2018; 18(1): 74.
[35]
Irie N, Weinberger L, Tang WW, Kobayashi T, Viukov S, Manor YS, et al. SOX17 is a critical specifier of human primordial germ cell fate. Cell 2015; 160(1-2): 253-68.
[36]
Fu DY, Tan HS, Wei JL, Zhu CR, Jiang JX, Zhu YX, et al. Decreased expression of SOX17 is associated with tumor progression and poor prognosis in breast cancer. Tumour Biol 2015; 36(10): 8025-34.
[37]
Balgkouranidou I, Karayiannakis A, Matthaios D, Bolanaki H, Tripsianis G, Tentes AA, et al. Assessment of SOX17 DNA methylation in cell free DNA from patients with operable gastric cancer. Association with prognostic variables and survival. Clin Chem Lab Med 2013; 51(7): 1505-10.


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Article Details

VOLUME: 14
ISSUE: 2
Year: 2019
Page: [170 - 176]
Pages: 7
DOI: 10.2174/1574892814666181231142136
Price: $58

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