<p>MicroRNA-34a suppresses aggressiveness of hepatocellular carcinoma by modulating <em>E2F1</em>, <em>E2F3</em>, and Caspase-3</p>

Abstract

Background: Accumulating evidence suggests an antineoplastic role of MicroRNA-34a ( miR-34a ) in human cancer. However, its precise biological functions stay largely elusive. Purpose: Our study was aimed to investigate the impact of miR-34a on hepatocellular carcinoma (HCC) and its underlying apoptosis related mechanisms in vitro, as well as the association of miR-34a , E2F1 and E2F3 expression with patient survival of HCC using publicly accessed datasets. Methods: The HBV-expressing Hep3B and SNU-449 cell lines with or without enforced expression of miR-34a were in vitro cultured for cell proliferation, colony formation, wound healing, cell invasion, and 3D spheroid formation. Quantitative reverse transcription PCR (RT-qPCR) was performed for E2F1, E2F3 expression. Caspase-3 (CASP3) activity was determined using a CaspACE TM Assay System. Kaplan–Meier survival curves were used to analyze the associations of miR-34a, E2F1 and E2F3 expression and overall survival in HCC. Meta-analysis was performed to examine the differential expression of E2F1 and E2F3 between primary HCC vs normal tissues. Results: The results in vitro showed that enforced miR-34a expression significantly inhibited cell proliferation, migration, and invasion of both Hep3B and SNU-449. RT-qPCR results demonstrated that miR-34a could significantly suppress E2F1 and E2F3 expression, particularly in SNU-449. CASP3 activity in both Hep3B and SNU-449 increased in miR-34a treatment group. Overexpressed E2F1 and E2F3 were observed in primary HCC vs normal tissues. Survival analyses showed that HCC patients with either high miR-34a , or low E2F1 , or low E2F3 expression had better survival than their opposite counterparts, respectively. Conclusion : Our study suggested that miR-34a can modulate the expression of E2F1, E2F3 , and CASP3 activity, thereby repressing tumor aggressiveness and expediting apoptosis in liver cancer cells

Peer Review #1 of "Identification of key genes and long non-coding RNA associated ceRNA networks in hepatocellular carcinoma (v0.2)"

“…(An et al 2015) E2F1 is a transcription factor that has been known to promote HCC progression. (Farra et al 2017) Besides the findings in this study, miR-331-3p (Jin et al 2019) and miR-34a (Han et al 2019) have also been found to regulate E2F1 expression in HCC cell lines. However, precise interactions between E2F1 and miRNAs need further exploration.…”

Molecular targets of Yangyin Fuzheng Jiedu Prescription in the treatment of hepatocellular carcinoma based on network pharmacology analysis

“…The antineoplastic activity of ESR1 has been also highlighted in a study of Chen et al, which validated its ability in impeding HCC cell growth and triggering cell apoptosis [ 39 ]. Besides, the malignancy of HCC cells could be halted by overexpression of CASP3, which could also improve the survival of HCC patients [ 40 ]. Corroborating findings have been identified in our study, which demonstrated that YFJP augmented HCC cell migration and invasion, and induced cell apoptosis through regulating these target genes.…”

<p>A Novel Circular RNA, circ_0005394, Predicts Unfavorable Prognosis and Contributes to Hepatocellular Carcinoma Progression by Regulating miR-507/E2F3 and miR-515-5p/CXCL6 Signaling Pathways</p>

“…28,29 What's more, E2F3 exerts oncogenic function in various cancers, including HCC. 30 CXCL6, also known as granulocyte chemotactic protein 2, was firstly found in MG63 cells, one of the osteosarcoma cell lines. CXCL6 regulates its downstream pathways via binding withC-X-C Motif Chemokine Receptor 1 (CXCR1) and C-X-C Motif Chemokine Receptor 2 (CXCR2).…”