MicroRNA‑466 inhibits the aggressive behaviors of hepatocellular carcinoma by directly targeting metadherin

Abstract

Numerous microRNAs (miRNAs) have been demonstrated to be downregulated or upregulated in hepatocellular carcinoma (HCC) and play important roles in its occurrence and development. Therefore, the investigation of miRNAs and their functions implicated in the genesis and development of HCC may provide key clues for the identification of effective therapeutic approaches for patients with this disease. The aims of the present study were to detect miRNA-466 (miR-466) expression in HCC tissues and cell lines and to determine its effects on HCC cell proliferation, apoptosis and metastasis, as well as to explore the mechanisms underlying the tumor-suppressing roles of miR-466 in HCC. In the present study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to detect miR-466 expression in HCC tissues and cell lines. The effects of miR-466 upregulation on HCC cell proliferation, apoptosis, migration and invasion were determined using Cell Counting Kit-8 assay, flow cytometry analysis and Transwell chamber assay, respectively. The potential target gene of miR-466 was predicted using bioinformatic analysis, which was further confirmed by luciferase reporter assay, RT-qPCR and western blot analysis. It was found that miR-466 was obviously decreased in HCC tissues and cell lines. The results of functional experiments revealed that restoration of miR-466 expression suppressed the proliferation, induced apoptosis, and reduced the metastasis of HCC cells. In addition, metadherin (MTDH) was identified as a direct target of miR-466 in HCC cells. Furthermore, MTDH was upregulated in HCC tissues, which was inversely correlated with the miR-466 level. Moreover, inhibition of MTDH displayed similar tumor-suppressing roles as miR-466 upregulation in HCC cells. In addition, MTDH reintroduction restored the tumor-suppressor activity of miR-466 overexpression in HCC cells. These findings suggest that miR-466 is a potential therapeutic tool for HCC therapy.

Wnt/β-Catenin Signaling as a Driver of Hepatocellular Carcinoma Progression: An Emphasis on Molecular Pathways

“… 177 miRNA-466 stimulates apoptosis and decreases growth capacity of HCC cells via down-regulating metadherin expression. 178 miRNA-466 can also affect Wnt/β-catenin signaling in HCC. Increasing miRNA-466 expression triggers apoptosis and diminishes growth and migration of HCC cells.…”

Integrative analysis of mRNA and miRNA sequencing data for gliomas of various grades

“…Increased expression of has-miR-466 inhibited the in vitro proliferation and invasion of osteosarcoma cells [55]. Similarly, a decrease in hsa-miR-466 expression has been demonstrated in hepatocellular carcinoma cells, and an increase in hsa-miR-466 expression inhibits proliferation, induces apoptosis and reduces the metastatic potential of the tumour by targeting MTDH [56]. In prostate cancer, a decrease in hsa-miR-466 expression was demonstrated due to the activity of the long noncoding RNA TUC338.…”

Long non‑coding RNA MBI‑52 inhibits the development of liver fibrosis by regulating the microRNA‑466g/SMAD4 signaling pathway

“…miRNAs are highly conserved RNAs that exhibit a high degree of homology between different species. Jia et al ( 37 ) demonstrated that miR-466 inhibits the aggressive behavior of hepatocellular carcinoma by directly targeting metadherin. However, the results of the present study demonstrated that knockdown of miR-466g reversed the activation of HSCs and the downregulation of α-SMA and Col-1 expression induced by lnc-MBI-52 knockdown.…”