MiR‐27a‐3p targets USP46 to inhibit the cell proliferation of hepatocellular carcinoma

Abstract

Micro‐RNAs are involved in the occurrence and development of hepatocellular carcinoma (HCC) as potential therapeutic targets for HCC. In this study, we found that miR‐27a‐3p was highly expressed in HCC, which was associated with lower survival rates of HCC patients. In vivo and in vitro functional experiments confirmed that over‐expression or knock‐down miR‐27a‐3p could significantly affect the proliferation ability of HCCLM3 and Huh‐7, two HCC cell lines. Ubiquitin‐specific protease 46 (USP46) was confirmed as the key target gene of miR‐27a‐3p in HCC via RNA‐seq, quantitative polymerase chain reaction, Western blotting, and luciferase report. When knocking down USP46, the proliferation activity of HCC cells was significantly enhanced, while it was significantly inhibited after over‐expressing USP4. Above results suggest that the abnormally over‐expressed miR‐27a‐3p in liver promotes the proliferation of cancer cells and accelerates the development of HCC by targeting inhibition the expression of USP46. Targeting miR‐27a‐3p may be an effective strategy for prevention and treatment of HCC.

CRISPR-Based Dissection of microRNA-23a~27a~24-2 Cluster Functionality in Hepatocellular Carcinoma

“…This involvement potentially encompasses two signaling axes: miR-23a-BMPR2 and miR-27a-TMEM170B in HCC cells. In conclusion, our CRISPRi/a study provides a valuable tool for comprehending the integrated roles and underlying mechanisms of endogenous miRNA clusters, paving the way for promising directions in miRNA-targeted therapy interventions.Nevertheless, investigations into the three mature miRNAs within the miR-23a ~ 27a ~ 24 − 2 cluster in HCC have reported inconsistent results for miR-23a 7-15 , miR-27a [16][17][18][19][20][21][22][23][24][25] , and miR-24 [26][27][28][29] . This inconsistency suggests their potential involvement in distinct cell signaling pathways, contributing to self-regulation and feedback loops under diverse circumstances 30,31 .Traditional methods involving overexpression through transfection with plasmids or RNA interference techniques may introduce exogenous variables, potentially leading to spurious effects and not accurately re ecting endogenous miRNA dynamics.…”

“…Nevertheless, investigations into the three mature miRNAs within the miR-23a ~ 27a ~ 24 − 2 cluster in HCC have reported inconsistent results for miR-23a 7-15 , miR-27a [16][17][18][19][20][21][22][23][24][25] , and miR-24 [26][27][28][29] . This inconsistency suggests their potential involvement in distinct cell signaling pathways, contributing to self-regulation and feedback loops under diverse circumstances 30,31 .…”