MicroRNA-424 inhibits Akt3/E2F3 axis and tumor growth in hepatocellular carcinoma

Abstract

By comparing the expression profiles of miRNAs in different subtypes of HCC, we identified miR-424 as a HCC related miRNA. We found that the expression of miR-424 was significantly decreased in HCC tissues and six liver cancer cell lines. Significantly, its expression levels were correlated with tumor size, multiple nodules, vein invasion, TNM stage and overall survival of HCC. We showed that up-regulated miR-424 suppressed HCC cell proliferation in vivo and in vitro. Multi-pathway reporter arrays suggested that miR-424 suppressed the pRb-E2F pathway. Consistently, Akt3 and E2F3 were identified as the targets of miR-424 as evidenced by that ectopic miR-424 expression suppressed Akt3 and E2F3 expressions. Silencing Akt3 and E2F3 by siRNA pheno-copied the effect of ectopic miR-424 on HCC growth. Whereas, overexpression of Akt3 and E2F3 attenuated the effect of miR-424 on HCC growth. Together, our data demonstrated a tumor suppressor role for miR-424 in HCC development and progression with therapeutic implications. The strong correlation of miR-424 expression with HCC patient survival suggests that miR-424 could be a valuable biomarker for HCC prognosis.

Loss of MiR‐424‐3p, not miR‐424‐5p, confers chemoresistance through targeting YAP1 in non‐small cell lung cancer

“…However, our findings were entirely consistent with Wu et al showed that miR‐424 could suppress invasion in bladder cancer . Furthermore, in vitro NSCLC cell lines, we found that miR‐424‐3p was able to prevent proliferation, which was in full agreement with the Yang et al demonstration in HCC that miR‐424 suppressed proliferation of HCC cells both in vivo and in vitro .…”

Baicalein, a Natural Anti-Cancer Compound, Alters MicroRNA Expression Profiles in Bel-7402 Human Hepatocellular Carcinoma Cells

“…For example, miR-191, an oncogenic miRNA, was shown to be highly expressed in HCC and involved in cell proliferation, apoptosis and epithelial mesenchymal transition in HCC, and its hypomethylation has been proved to be associated with poor prognosis [32], interestingly, here we found miR-191 could be down-regulated by baicalein; miR-222-5p and miR-675 were reported to be up-regulated in HCC tumor tissues and positively associated with recurrence after resection [33], whereas our result showed that they were both down-regulated under baicalein treatment; miR-424-3p has been demonstrated to be down-regulated in HCC and suppresses tumor growth, cell migration and invasion through its downstream target Akt3, E2F3 and c-Myb [34, 35], nevertheless, we found miR-424-3p could be up-regulated by baicalein. In addition, previous studies have demonstrated that baicalein is able to inhibit the proliferation, invasion and metastasis of HCC through inducing cell cycle arrest and apoptosis via several cancer-related signaling including MEK/ERK, JNK, mTOR, NF-κB etc [5, 6].…”

Biomarker MicroRNAs for Diagnosis, Prognosis and Treatment of Hepatocellular Carcinoma: A Functional Survey and Comparison

“…miR-101-3p, miR-106-5p, miR-17-5p, miR-18b-5p, miR-21-5p, miR-25-3p and miR-331-3p) and low expression of seven miRNAs ( i.e. miR-125a-5p, miR-128-3p, miR-188-5p, miR-206, miR-212-3p, miR-424-5p and miR-744-5p) were outstandingly correlated with limitless replicative potential and could provide positive prognostic values for HCC3846474852566465697073747687. Four prognostic circulating miRNAs associated with proliferation and limitless replicative potential, including miR-101-3p, miR-122-5p, miR-21-5p and miR-331-3p, were reported up-regulated in HCC patients38566177.…”