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12 July 2019 : Clinical Research

Inhibition of MicroRNA-381 Promotes Tumor Cell Growth and Chemoresistance in Clear-Cell Renal Cell Carcinoma

Yunhui Chan1BCDEF, Yipeng Yu2BCDF, Gang Wang2BCF, Changlin Wang2BCF, Daming Zhang34BCF, Xiaoxiong Wang4BF, Zichun Wang2BC, Wengang Jian2BC, Cheng Zhang2ADE

DOI: 10.12659/MSM.915524

Med Sci Monit 2019; 25:5181-5190

Abstract

BACKGROUND: MicroRNA-381 (miR-381) is proven to be involved in many human tumors. Bioinformatics prediction suggests that miR-381 is decreased in renal cell carcinoma. However, its biological functions in clear-cell renal cell carcinoma (ccRCC) remain largely unknown. The present research aimed to evaluate miR-381 expression in renal cancer tissues and its effects on cell proliferation, growth, migration, and chemoresistance.

MATERIAL AND METHODS: Sixty pairs of ccRCC and the adjacent non-tumor specimens were collected during routine therapeutic surgery. Quantitative real-time PCR (qRT-PCR) assay was employed to examine miR-381 expression in the ccRCC tissues and the associated adjacent tissues (the normal tissues adjacent to tumor tissues). Cell transfection assay and Thiazolyl Blue Tetrazolium Bromide (MTT) assay were utilized to observe effects of miR-381 on the cell proliferation, growth, invasion, and chemoresistance in the Caki-1 cell line and 786-O cell line. Flow cytometry was used to assess cell apoptosis. Caki-1 cell and 786-O cell Xenograft BALB/c mouse models were established.

RESULTS: miR-381 expression was downregulated in ccRCC tissues in vivo and in cell lines in vitro. Downregulation of miR-381 promoted growth of cells and restrained the ccRCC cell apoptosis. Increased miR-381 combined with Ci and Pa suppressed the proliferation and enhanced the anti-tumor effects of Ci and Pa at tolerated concentrations in vitro. miR-381 inhibition promoted chemoresistance in vitro.

CONCLUSIONS: miR-381 levels were significantly downregulated in renal cancer tissues and miR-381 inhibition promoted tumor cell growth, migration, and chemoresistance.

Keywords: Carcinoma, Renal Cell, Chemotherapy, Adjuvant, Drug Resistance

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750