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微小RNA-613通过靶向SOX9表达诱导胃癌细胞对顺铂的敏感性。

MicroRNA-613 induces the sensitivity of gastric cancer cells to cisplatin through targeting SOX9 expression.

作者信息

Xue Minghui, Li Guangyan, Sun Peisheng, Zhang Dezhong, Fang Xiangjie, Li Wei

机构信息

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Xinxiang Medical University Weihui 453100, Henan, China.

Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical University Weihui 453100, Henan, China.

出版信息

Am J Transl Res. 2019 Feb 15;11(2):885-894. eCollection 2019.

Abstract

Increasing evidences have suggested that deregulated miRNAs may involve in drug chemoresistance in a lot of human cancers. However, the role of miR-613 in drug chemoresistance of GC cell is still unknown. The expression of miR-613 and Sex-determining region Y (SRY)-box 9 (SOX9) in GC tissues and cell lines was detected by using qRT-PCR. Cell migration and viability were measured by the wound healing assay and CCK-8 assays. Western blot and dual-luciferase reporter were done to identify the target gene of miR-613. We showed that miR-613 expression was downregulated in GC tissues and cell lines. Ectopic expression of miR-613 increased the sensitivity of GC cells to cisplatin. Overexpression of miR-613 suppressed GC cell proliferation, cycle and migration. In addition, we identified SOX9 was a direct target gene of miR-613 in GC cell. We showed that SOX9 expression was upregulated in gastric cancer samples. Moreover, the expression of SOX9 was negatively correlated with miR-613 expression in GC tissues. Furthermore, elevated expression of miR-613 increased the sensitivity of GC cells to cisplatin and suppressed GC cell proliferation and migration by targeting SOX9. These data suggested that miR-613 might function as a chemoresistant suppressor in GC.

摘要

越来越多的证据表明,失调的微小RNA(miRNA)可能参与多种人类癌症的化疗耐药。然而,miR-613在胃癌(GC)细胞化疗耐药中的作用仍不清楚。采用qRT-PCR检测miR-613和性别决定区Y(SRY)-盒9(SOX9)在GC组织和细胞系中的表达。通过伤口愈合试验和CCK-8试验检测细胞迁移和活力。进行蛋白质免疫印迹法(Western blot)和双荧光素酶报告基因检测以鉴定miR-613的靶基因。我们发现miR-613在GC组织和细胞系中的表达下调。miR-613的异位表达增加了GC细胞对顺铂的敏感性。miR-613的过表达抑制了GC细胞的增殖、周期和迁移。此外,我们鉴定出SOX9是GC细胞中miR-613的直接靶基因。我们发现SOX9在胃癌样本中的表达上调。此外,在GC组织中SOX9的表达与miR-613的表达呈负相关。此外,miR-613表达的升高通过靶向SOX9增加了GC细胞对顺铂的敏感性,并抑制了GC细胞的增殖和迁移。这些数据表明,miR-613可能在GC中作为化疗耐药抑制因子发挥作用。

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