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抗 miR-197 通过靶向 KAI1/CD82 抑制 HCC 细胞迁移。

Anti-miR-197 inhibits migration in HCC cells by targeting KAI 1/CD82.

机构信息

Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China.

Department of Gastroenterology, Tong Ren Hospital, Jiaotong University, School of Medicine, Shanghai, China.

出版信息

Biochem Biophys Res Commun. 2014 Apr 4;446(2):541-8. doi: 10.1016/j.bbrc.2014.03.006. Epub 2014 Mar 12.

Abstract

AIM

To investigate the metastatic effects and mechanisms of miR-197 in hepatocellular carcinoma (HCC).

METHODS AND RESULTS

The levels of miR-197 increased in HCC cells and tissues compared with a normal hepatic cell line (LO2) and adjacent nontumorous liver tissues, respectively. miR-197 expression negatively correlated with CD82 mRNA expression in these cell lines and tissues. Dual luciferase reporter assay and Western blot confirmed a direct interaction between miR-197 and CD82 3'UTR sequences. After miR-197 was silenced in HCC cells, CD82 expression increased. In the presence of human hepatocyte growth factor (HGF), cells silenced for anti-miR-197 exhibited elongated cellular tails and diminished lamellipodia due to reductions in both ROCK activity and the levels of Rac 1 protein. Downregulation of miR-197 along with the upregulation of CD82 in HCC cells resulted in the inhibition of HCC migration and invasion in vitro and in vivo.

CONCLUSION

Taken together, these data suggest that anti-miR-197 suppresses HCC migration and invasion by targeting CD82. The regulation of the miR-197/CD82 axis could be a novel therapeutic target in future HCC effective therapy.

摘要

目的

研究 miR-197 在肝细胞癌(HCC)中的转移作用及其机制。

方法与结果

与正常肝细胞系(LO2)和相邻非肿瘤性肝组织相比,HCC 细胞和组织中的 miR-197 水平升高。miR-197 表达与这些细胞系和组织中的 CD82 mRNA 表达呈负相关。双荧光素酶报告基因检测和 Western blot 证实了 miR-197 与 CD82 3'UTR 序列的直接相互作用。在 HCC 细胞中沉默 miR-197 后,CD82 表达增加。在人肝细胞生长因子(HGF)存在的情况下,抗 miR-197 沉默的细胞由于 ROCK 活性和 Rac 1 蛋白水平降低而表现出长细胞尾和减少片状伪足。HCC 细胞中 miR-197 的下调和 CD82 的上调导致 HCC 在体外和体内迁移和侵袭的抑制。

结论

综上所述,这些数据表明,抗 miR-197 通过靶向 CD82 抑制 HCC 的迁移和侵袭。miR-197/CD82 轴的调节可能成为未来 HCC 有效治疗的新治疗靶点。

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