miR-4458 inhibits the epithelial-mesenchymal transition of hepatocellular carcinoma cells by suppressing the TGF-β signaling pathway via targeting TGFBR1

• 作者: Hang Liu Kun Shi Wei Chen Xufu Wei Yuke Zhang Yunhai Luo Zhongjun Wu
• 来源期刊: 生物化学与生物物理学报（英文版）
• 关键词: miR-4458 hepatocellular carcinoma epithelial-mesenchymal transition TGFBR1
• 年，卷（期）: 2020,（5）
• 页码范围: 554-562
• 页数: 9页
• 语种: 英文
• DOI: 10.1093/abbs/gmaa029

摘要

Hepatocellular carcinoma (HCC) is one of the most lethal cancers in the world.MicroRNAs play a pivotal role in the progression of various cancers.To date,very little attention has been paid to miR4458.Therefore,the aim of our study was to explore the function and underlying molecular mechanism of miR-4458 in HCC.We found that the expression of miR-4458 was reduced in HCC tissues and cell lines.Forced overexpression of miR-4458 inhibited the migration,invasion,and epithelialmesenchymal transition (EMT) of HCC cells,while downregulation of miR-4458 promoted the aggressive phenotype.Furthermore,transforming growth factor beta receptor 1 (TGFBR1),the modulator of the TGF-β signaling pathway,was verified to be a novel target gene of miR-4458 by dual-luciferase reporter gene assay.Upregulated miR-4458 dramatically abolished TGFBR1 and p-Smad2/3 expression,thus blocking the TGF-β signaling pathway.Moreover,restoration of TGFBR1 partially rescued the miR-4458-mediated suppressive effect on the migration,invasion,and EMT and reactivated the TGF-β signaling pathway in HCC cells.In summary,our findings first demonstrated a mechanism of miR-4458 in HCC cell migration,invasion,and EMT by regulating the TGF-β signaling pathway via directly targeting TGFBR1.