Department of Infectious Disease, Heping Hospital Attached to Changzhi Medical College, Changzhi, 046000, China.
Changzhi Medical College, Changzhi, 046000, China.
Exp Cell Res. 2019 Jul 15;380(2):124-130. doi: 10.1016/j.yexcr.2019.03.042. Epub 2019 Apr 4.
Aberrant miR-629-5p expression in several cancer types has been reported. Nonetheless, its potential effect and mechanism of action on tumor growth and metastasis in hepatocellular carcinoma (HCC) have rarely been analyzed. In this study, we found that miR-629-5p was upregulated in HCC tissue samples as compared to matched adjacent-tissue samples. Overexpression of miR-629-5p promoted the proliferation, migration, and invasiveness of human HCC cells in vitro, whereas miR-629-5p knockdown reduced these parameters. Consistently, miR-629-5p overexpression accelerated tumor growth and metastasis in a nude mouse model. Mechanistically, miR-629-5p directly targeted the 3' untranslated region (3'UTR) of the secreted frizzled-related protein 2 (SFRP2) mRNA and suppressed its expression, resulting in the activation of β-catenin. Inhibition of β-catenin abrogated miR-629-5p-induced growth and invasiveness. Collectively, these results suggest that miR-629-5p activates β-catenin signaling by downregulating SFRP2 and thus promotes the growth and metastasis of HCC. These data open up new prospects for HCC treatment.
已有研究报道,多种癌症类型中存在 miR-629-5p 的异常表达。然而,其在肝细胞癌(HCC)中对肿瘤生长和转移的潜在作用及机制仍鲜有分析。本研究发现,与配对的癌旁组织样本相比,miR-629-5p 在 HCC 组织样本中呈上调表达。miR-629-5p 的过表达促进了人 HCC 细胞在体外的增殖、迁移和侵袭,而 miR-629-5p 的敲低则降低了这些参数。一致地,miR-629-5p 的过表达在裸鼠模型中加速了肿瘤的生长和转移。在机制上,miR-629-5p 可直接靶向分泌型卷曲相关蛋白 2(SFRP2)mRNA 的 3'非翻译区(3'UTR)并抑制其表达,导致 β-连环蛋白的激活。β-连环蛋白的抑制可阻断 miR-629-5p 诱导的生长和侵袭。综上,这些结果表明,miR-629-5p 通过下调 SFRP2 激活 β-连环蛋白信号通路,从而促进 HCC 的生长和转移。这些数据为 HCC 的治疗提供了新的前景。