MiR-518b Promotes the Tumorigenesis of Hepatocellular Carcinoma by Targeting EGR1 to Regulate PI3K/AKT/mTOR Signaling Pathway.

Abstract

Hepatocellular carcinoma (HCC) is a prevalent malignancy originating from hepatocytes and is characterized by high invasiveness and fatality. Dysregulation of microRNAs (miRNAs) is frequently observed during HCC progression. This study aimed to investigate the role of miR-518b in HCC cell malignancy and tumor growth. MiR-518b expression in HCC cells was measured by RT-qPCR. The proliferative, migratory and invasive capabilities of Hep3B and SNU-387 were assessed by colony formation, wound healing and transwell assays, respectively. RNA immunoprecipitation and luciferase reporter assays were utilized to verify the binding between miR-518b and its target gene, early growth response factor 1 (EGR1). Results revealed that miR-518b was highly expressed while EGR1 was downregulated in HCC cells. Knockdown of miR-518b significantly repressed cell proliferation, migration and invasion. Moreover, miR-518b bound to 3'untranslated region of EGR1 and negatively regulated its expression in HCC cells. EGR1 knockdown counteracted the inhibitory impact of miR-518b inhibition on malignant cell behaviors. In addition, the silencing of EGR1 activated the PI3K/AKT/mTOR signaling in HCC cells, while miR-518b depletion had the opposite effect. Importantly, the suppressive impact of miR-518b on the pathway was rescued by EGR1 knockdown. In vivo experiments demonstrated that inhibition of miR-518b suppressed HCC tumor growth, reduced EGR1 and Ki67 (a proliferation marker) expression, and inactivated the PI3K/AKT/mTOR signaling. In conclusion, miR-518b promotes HCC tumorigenesis by targeting EGR1 and regulating the PI3K/AKT/mTOR signaling pathway.