Tumor-Suppressing Effect of MiR-4458 on Human Hepatocellular Carcinoma

Abstract

Background: Besides multiple genetic and epigenetic changes of protein coding genes in hepatocellular carcinoma (HCC), growing evidence indicate that deregulation of miRNAs contribute to HCC development by influencing cell growth, apoptosis, migration, or invasion. IKBKE is amplified and over-expressed in a large percentage of human breast tumors and identified as an oncogene of human breast tumor. Microarray analysis showed that miR-4458 was down-regulated in HCC tissues. Methods: The level of miR-4458 was up-regulated by miR-4458 mimics transfection, or down-regulated by miR-4458 ASO transfection. Cell proliferation was assayed by MTT analysis. MiRNAs and mRNA expression were assayed by qRT-PCR. These potential targeted genes of miR-4458 were predicted by bioinformatic algorithms. Dual luciferase reporter assay system was used to analyze the interaction between miR-4458 and IKBKE. IKBKE protein level was assayed by Western blot. The role of miR-4458 or IKBKE in the survival of HCC patients were revealed by Kaplan-Meier plot of overall survival. Results: Lower miR-4458 expression level or higher IKBKE level in HCC tissues correlated with worse prognosis of HCC patients. Overexpression of miR-4458 inhibited the HCC cells growth and vice versa. MiR-4458 played its role via targeting 3'UTR of IKBKE. Conclusions: MiR-4458 or IKBKE may be potential predictors of HCC prognosis. Restoration of miR-4458 or inhibition of IKBKE could be a prospective therapeutic approach for HCC.

MicroRNA-4458 suppresses the proliferation of human lung cancer cells in vitro by directly targeting Lin28B

“…Recently, two studies indicated that miR-4458 is a tumor suppressor that is down-regulated in human hepatocellular carcinoma and colon cancer and might influence cell viability in these two cancer types [12,13] . Moreover, miR-4458 was shown to be a potential prognosis predictor for hepatocellular carcinoma patients [12] and inhibited glycolysis and lactate production in colon cancer cells [13] . Mechanistically, direct interaction between miR-4458 and the 3'UTR of IKBKE or HK2 mRNA was identified in cancer cells.…”

“…Previous studies have indicated that miR-4458 expression is dysregulated in hepatocellular carcinoma [12] and colon cancer [13] . Those studies reported that miR-4458 is a tumor suppressor that is down-regulated in hepatocellular carcinoma and colon cancer, and that the high expression of miR-4458 suppresses the proliferation of tumor cells [12,13] . However, the role of miR-4458 in NSCLC remains unclear.…”

“…However, the role of miR-4458 in NSCLC remains unclear. Although certain target genes of miR-4458 have been predicted and detected in other types of cancer cells [12,13] , the direct target of miR-4458 and its function in lung cancer remains to be studied. Bioinformatics analysis predicted that miR-4458 could directly bind to the 3'UTR of Lin28B, which is frequently overexpressed in various cancers, including lung cancer, and is associated with the induction of tumorigenesis [14][15][16] .…”

Atmospheric particulate matter2.5 promotes the migration and invasion of hepatocellular carcinoma cells

“…Hepatocellular carcinoma (HCC) is one of the predominant causes of cancer-associated mortality worldwide (8). HCC cell metastasis is the primary cause of HCC development.…”

Isocitrate Dehydrogenase 2 Suppresses the Invasion of Hepatocellular Carcinoma Cells via Matrix Metalloproteinase 9

“…In spite of the continuous increases in 5-year survival for HCC due to advances in combined therapy with surgery, radiotherapy and chemotherapy, some patients still suffer from poor outcome due to malignant growth and metastases of HCC [1][2][3][4]. Thus, a further understanding of the molecular mechanisms underlying the progression and metastases of HCC would improve the current therapy [5][6][7][8][9][10][11][12][13].…”