Up-regulated MicroRNA-181a induces carcinogenesis in Hepatitis B virus-related hepatocellular carcinoma by targeting E2F5

Abstract

BackgroundAccumulating evidence showed that microRNAs are involved in development and progression of multiple tumors. Recent studies have found that miR-181a were dysregulated in several types of cancers, however, the function of miR-181a in hepatocellular carcinoma (HCC) remains unclear. In this study we assessed the potential association between miR-181a, HBV and HCC.MethodsThe expression of miR-181a in HBV-expressing cells was determined by using qRT-PCR. Dual-Luciferase reporter Assay, qRT-PCR and western blot were performed to investigate the target genes of miR-181a. The effects of miR-181a on HCC proliferation were analyzed by MTS and colony formation assay. Tumor growth assay was used to analyze the effect of miR-181a on tumor formation.ResultsHBV up-regulated miR-181a expression by enhancing its promoter activity. Overexpression of miR-181a in hepatoma cells promoted cell growth in vitro and tumor formation in vivo. Conversely, inhibition of miR-181a suppressed the proliferation of HBV-expressing cells. Mechanism investigation revealed that miR-181a inhibited the expression of transcription factor E2F5 by specifically targeting its mRNA 3′UTR. Moreover, E2F5 inhibition induced cell growth and rescued the suppressive effect of miR-181a inhibitor on the proliferation of SMMC-7721 cells. Interestingly, we also discovered that HBV could down-regulate E2F5 expression.ConclusionsThose results strongly suggested that HBV down-regulated E2F5 expression, in part, by up-regulating the expression of miR-181a. Up-regulation of miR-181a by HBV in hepatoma cells may contribute to the progression of HCC possibly by targeting E2F5, suggesting miR-181a plays important role in HCC development.

miR-429 represses cell proliferation and induces apoptosis in HBV-related HCC

“…MiR-122, a special miRNA of liver had been found to downregulate after HBV infection in several studies [13]. In addition, miRNA, including miR-1 [14], miR-181a [15], miR-372 [16], miR-501 [17], was reported to upregulate after HBV infection. Moreover, some miRNAs have been identified to vary according to the development level of disease.…”

MicroRNA-133a inhibits cell proliferation, colony formation ability, migration and invasion by targeting matrix metallopeptidase 9 in hepatocellular carcinoma

“…The cell migration and invasion were assayed using Transwell ® chambers (8 µm; Corning Costar, Cambridge, MA, USA). For the Transwell ® migration assay, 1x10 5 transfected cells (miR 133a mimics and NC) were placed into the upper chamber, which was cultured in medium with 2% FBS, while 500 µl RPMI-1640 medium containing 20% FBS was added to the lower chamber. For the Transwell ® invasion assay, a Transwell ® chamber coated with Matrigel ® (BD Biosciences, San Jose, CA, USA) and a total of 1x10 5 cells were seeded into the upper chamber, while the lower chamber was incubated with 500 µl RPMI-1640 medium containing 20% FBS.…”

“…HCC accounts for between 85 and 90% of all cases of primary liver cancer and is the third leading cause of mortality from cancer worldwide and the fifth most common type of malignancy (1)(2)(3)(4). It has been reported that ~21,000 cases of HCC are diagnosed and ~700,000 patients succumb to the disease worldwide annually (5). The established risk factors of HCC include viral hepatitis, alcohol abuse and non-alcoholic fatty liver disease (6).…”

Hsa-microRNA-181a is a regulator of a number of cancer genes and a biomarker for endometrial carcinoma in patients: a bioinformatic and clinical study and the therapeutic implication

“…As in glioblastoma, significant downregulation of hsa-miR-181a was also observed in squamous lung cell carcinoma,83 oral squamous cell carcinoma,71 luminal A-like breast cancer,67 and non-small-cell lung cancer 84. However, hsa-miR-181a was significantly overexpressed in MCF-7 breast cancer cells,85 colorectal cancer,28 and hepatocellular carcinoma cells 56,86,87. Hsa-miR-181a was upregulated in acute myeloid leukemia,76 especially in the M1 and M2 subtypes, and in myelodysplastic syndromes88 but downregulated in multiple myeloma89 and chronic lymphocyte leukemia 79,90.…”