MicroRNA-582-3p targeting ribonucleotide reductase regulatory subunit M2 inhibits the tumorigenesis of hepatocellular carcinoma by regulating the Wnt/beta-catenin signaling pathway

Hepatocellular carcinoma (HCC) is an important cause of death worldwide. MicroRNA (miRNA)-mediated gene silencing is involved in tumor biology. In this study, we aimed to elucidate the function and mechanism of action of miR-582-3p in HCC. We performed reverse transcription-quantitative polymerase chain reaction and western blotting to detect the expression levels of miR-582-3p, ribonucleotide reductase regulatory subunit M2 (RRM2), and markers of the Wnt/beta-catenin signaling pathway (Wnt, Gsk-3 beta, beta-catenin, and C-myc). The potential binding between miR-582-3p and RRM2 was confirmed using a dual-luciferase reporter assay. The proliferative and migratory capacities of the cells were evaluated using the cell counting kit-8 and wound-healing assays, respectively. Mouse models were used to validate the role of miR-582-3p in vivo. We observed the downregulation of miR-582-3p levels in HCC tumors and cell lines. Its upregulation in Huh7 and Hep 3B cells impaired their proliferation and migration, and the in vivo results showed suppressed tumor growth. Additionally, miR-582-3p upregulation also reduced the expression levels of Wnt, beta-catenin, and C-myc, but enhanced the expression levels of glycogen synthase kinase-313, both in vitro and in vivo. miR-582-3p targeted RRM2, and a negative correlation was observed in its expression patterns in HCC. Furthermore, RRM2 overexpression aggravated the proliferative and migratory capabilities of Hep3B and Huh7 cells and triggered Wnt/beta-catenin signaling. However, miR-582-3p depleted RRM2 expression, thereby attenuating the oncogenic effects of RRM2. In conclusion, our results demonstrated that miR-582-3p binds to RRM2 to regulate the Wnt/beta-catenin signaling pathway, thereby blocking the progression of HCC. [GRAPHICS] .

Automated summary

In this study, the researchers investigated the role of miR-582-3p in hepatocellular carcinoma (HCC) and found that its upregulation inhibited the proliferation and migration of HCC cells and suppressed tumor growth. They also discovered that miR-582-3p regulates the Wnt/β-catenin signaling pathway by targeting RRM2, thereby blocking the progression of HCC.