miR-182-5p promotes hepatocellular carcinoma progression by repressing FOXO3a

Abstract

BackgroundHigh frequency of recurrence is the major cause of the poor outcomes for patients with hepatocellular carcinoma (HCC). microRNA (miR)-182-5p emerged as a high-priority miRNA in HCC and was found to be related to HCC metastasis. Whether the expression of miR-182-5p in tumor tissue correlated with early recurrence in HCC patients underwent curative surgery was unknown.MethodsReal-time PCR (RT-PCR) and in situ hybridization (ISH) were conducted to assess the expression of miR-182-5p in HCC cells and tissues. Cell Counting Kit-8 (CCK-8), transwell assays were performed to detected cells proliferation and migration ability. Flow cytometry assays were used to detect cell apoptosis rate, and xenograft model was employed to study miR-182-5p in HCC growth and lung metastasis. The target of miR-182-5p was validated with a dual-luciferase reporter assay and western blotting. Immunohistochemistry, immumoblotting, and immunoprecipitation were performed to test relative protein expression.ResultsWe showed that high expression of miR-182-5p in tumor tissues correlated with poor prognosis as well as early recurrence in HCC patients underwent curative surgery. miR-182-5p enhanced motility and invasive ability of HCC cells both in vitro and in vivo. miR-182-5p directly targets 3′-UTR of FOXO3a and repressed FOXO3a expression, activating AKT/FOXO3a pathway to promote HCC proliferation. Notably, miR-182-5p activated Wnt/β-catenin signaling by inhibiting the degradation of β-catenin and enhancing the interaction between β-catenin and TCF4 which was mediated by repressed FOXO3a.ConclusionsConsistently, miR-182-5p can be a potential predictor of early recurrence for HCC patients underwent curative surgery, and FOXO3a plays a key mediator in miR-182-5p induced HCC progression.

P7TP3 inhibits tumor development, migration, invasion and adhesion of liver cancer through the Wnt/β‐catenin signaling pathway

“…TargetScan, micro‐RNA.org, miRDB and TargetMiner all predicted that miR‐182‐5p potentially binds to sequence in the 3′‐UTR of P7TP3.TargetScan, micro‐RNA.org, miRDB and TargetMiner predicted potential binding of miR‐182‐5p to sequence in 3′‐UTR of P7TP3. More importantly, miR‐182‐5p promoted HCC progression, and activated the Wnt/β‐catenin signaling pathway via FOXO3a . According to these results, miR‐182‐5p inhibited HCC by targeting P7TP3 through the Wnt/β‐catenin signaling pathway.…”

“…Moreover, miR‐182‐5p is considered a potential carcinogen as well as a prognostic factor in HCC. Until now, several target genes have been scanned for miR‐182‐5p in HCC, such as LINC01018 and FOXO3a . We herein provided a novel target gene for miR‐182‐5p (Figure ), which acts as a promising tumor suppressor.…”

“…For example, upregulation of miR‐182 in human osteosarcoma inhibited cancer progression and activated the Wnt/β‐catenin signaling pathway by targeting HOXA9 . miR‐182‐5p also contributed to HCC metastasis by activating the Wnt/β‐catenin signaling pathway through FOXO3a …”

miR-182-5p Promotes Growth in Oral Squamous Cell Carcinoma by Inhibiting CAMK2N1

“…In glioblastoma, miR-182-5p targets protein phosphatase 1 regulatory inhibitor subunit 1C [20]. miR-182-5p promotes the progression of hepatocellular carcinoma by repressing FOXO3a expression [21]. By down-regulating RAB27A expression, miR-182-5p improves the migration, mitosis, viability, and invasion capabilities of human gastric cancer cells [22].…”

Serum miR‐182 is a predictive biomarker for dichotomization of risk of hepatocellular carcinoma in rats

“…Functionally, this miRNA targets tumor suppressor genes CCAAT enhancer‐binding protein and forkhead box O 1 (FOXO1) . It has been also shown to affect WNT/β‐catenin and AKT signaling by targeting forkhead box O 3a (FOXO3a) in tumor tissue, which resulted in HCC proliferation . Within this study, increased miR‐182 could be altering these signaling pathways and increasing tumor cell proliferation.…”