miR-182 controls cell growth in gastrointestinal stromal tumors by negatively regulating CYLD expression

miR-182 通过负向调节 CYLD 表达来控制胃肠道间质瘤细胞的生长

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作者:Tianlong Ling, Fengrong Yu, Hui Cao

Abstract

Gastrointestinal stromal tumors (GISTs) are the most common type of mesenchymal tumor of the digestive tract. MicroRNAs (miRNAs) are short non-coding RNAs, which control gene expression at a post-transcriptional level. Dysregulated miRNAs are involved in various types of human disease, including cancer. In the present study, it was revealed that miRNA-182 (miR-182) expression was significantly upregulated in human GISTs compared with adjacent normal tissues. Overexpression of miR-182 enhanced GIST-T1 cell growth, with increased proliferation and decreased apoptosis. miR-182 upregulation also promoted colony formation and migration of GIST-T1 cells. In addition, cylindromatosis (CYLD) was identified as a direct target of miR-182. Overexpression of miR-182 suppressed CYLD expression and enhanced downstream nuclear factor (NF)-κB activation. It was also determined that the expression of CYLD was downregulated in association with upregulated miR-182 in human GISTs. In conclusion, these results demonstrated that miR-182 promoted GIST cell growth by negatively regulating CYLD expression. These findings indicated that miR-182 antagonist may be a promising therapeutic strategy for the treatment of human GIST.

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