MiR-466 Inhibits the Progression of Severe Hepatocellular Carcinoma via Regulating FMNL2-Mediated Activation of NF-κB and Wnt/β-Catenin Pathways

Abstract

Hepatocellular carcinoma (HCC) has threatened the health of humans, and some evidence has indicated that miR-466 involves the progressions of some cancers. This study focused on the role of miR-466 in the formation and development of HCC. The expression levels of miR-466 in the tissues of patients and HCC cell lines were measured by qRT-PCR, and CCK-8, transwell assay, and flow cytometry assay were used to observe the functions of miR-466 on the HCC cells. Moreover, the miRNA databases, dual-luciferase reporter assay, and Western blot were used for the investigation of the regulation mechanism of miR-466 on HCC cells. The results showed that miR-466 was significantly downregulated in HCC tissues and cell lines, and inhibited proliferation, invasion, and high apoptosis were found in HCC cells when miR-466 was overexpressed. The results confirmed that FMNL2 was a target of miR-466, and increased FMNL2 could reverse the effects of miR-466 on the phenotype of HCC cells. Besides, it was also found that miR-466 was involved in the regulation of NF-κB and Wnt/β-catenin pathways in HCC cells via targeting FMNL2. In conclusion, the results of this study suggest that miR-466 regulates the activities of NF-κB and Wnt/β-catenin pathways to inhibit the progression of HCC cells via targeting FMNL2.

miR-211-5p Alleviates the Myocardial Ischemia Injury Induced by Ischemic Reperfusion Treatment via Targeting FBXW7

“…It has been found that FBXW7 serves as an inhibitor to suppress the activation of Wnt pathway in lung cancer [11]. Hence, this study sustains that attenuated miR-211-5p can promote the injury and apoptosis of myocardial cells suffering I/R via regulating FBXW7 mediated the inactivation of Wnt pathway [12].…”

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

“…At molecular level, miRNA-466 decreases FMNL2 expression to inhibit β-catenin signaling. 179 Notably, miRNA/β-catenin axis can also be affected by anti-tumor agents. A recent has revealed anti-tumor activity of astragaloside IV in HCC therapy.…”

WNT/β-catenin signaling in hepatocellular carcinoma: The aberrant activation, pathogenic roles, and therapeutic opportunities

“…109 miRNA-466 exerts its inhibitory effects on HCC progression by regulating formin-like 2 (FMNL2)-mediated activation of WNT/β-catenin signaling. 110 Indirect inhibitory effects on the WNT/β-catenin pathway impairing HCC growth and metastasis have been demonstrated for miRNA-26 b, miRNA-342, and miRNA-186. miRNA26b inhibits the expression of zinc ribbon domain-containing 1 (ZNRD1).…”