Decrease expression of microRNA-744 promotes cell proliferation by targeting c-Myc in human hepatocellular carcinoma

Abstract

BackgroundMicroRNAs (miRNAs) are a large group of post-transcriptional gene regulators that potentially play a critical role in tumorigenesis. Increasing evidences indicate that miR-744 deregulated in numerous human cancers including hepatocellular carcinoma (HCC). However, its role in HCC carcinogenesis remains poorly defined. In this study, we investigated the roles of miR-744 in tumor growth of HCC.MethodsQuantitative reverse-transcription polymerase chain reaction (qRT-PCR) was conducted to detect the expression of miR-744 and Immunohistochemistry was performed to detect expression of c-Myc in HCC specimens and adjacent normal tissues. The biological functions of miR-744 were determined by cell proliferation and cell cycle assay. Furthermore, cell lines transfected with miR-744 mimics were analyzed in vitro. Luciferase reporter assays was performed to confirm whether miR-744 regulated the expression of c-Myc.ResultsOur results showed that the expression of miR-744 was frequently down-regulated in both HCC tissues and cells. Furthermore, restoration of miR-744 in HCC cells was statistically correlated with decrease of cell growth and restored G1 accumulation. Luciferase assay and Western blot analysis revealed that c-Myc is a direct target of miR-744. Down-regulation of miR-744 and up-regulation of c-Myc were detected in HCC specimens compared with adjacent normal tissues. Moreover, restoration of miR-744 rescues c-Myc induced HCC proliferation.ConclusionsOur data suggest that miR-744 exerts its tumor suppressor function by targeting c-Myc, leading to the inhibition of HCC cell growth. miR-744 may serve as a potentially useful target for the miRNA-based therapies of HCC in the future.

MicroRNA-195a-5p inhibits mouse medullary thymic epithelial cells proliferation by directly targeting Smad7

“…For example, Cyclin D1 and E1 are related to the control of G1/S phase in cell cycle progression [45]. C-myc is indispensable for regulating cell growth, proliferation and development [46,47]. C-myc was also reported to be necessary for skin keratinocytes proliferation [27].…”

MIR744 (microRNA 744)

“…Under-expression of miR-744-5p was observed in HCC tissues compared with the normal counterparts (Tan et al, 2014;Lin et al, 2014). Furthermore, reduced miR-744-5p exhibited a significant linkage with HCC cases demonstrating multiple tumor nodes or microvascular invasion (Tan et al, 2014).…”

“…Furthermore, reduced miR-744-5p exhibited a significant linkage with HCC cases demonstrating multiple tumor nodes or microvascular invasion (Tan et al, 2014). In HCC cell lines with low endogenous miR-744-5p expression, introduction of miR-744 mimics reduced HCC growth (Lin et al, 2014). Using luciferase reporter assays, it was demonstrated that miR-744-5p was able to suppress the HCC cell growth by targeting c-Myc (Lin et al, 2014).…”

“…In HCC cell lines with low endogenous miR-744-5p expression, introduction of miR-744 mimics reduced HCC growth (Lin et al, 2014). Using luciferase reporter assays, it was demonstrated that miR-744-5p was able to suppress the HCC cell growth by targeting c-Myc (Lin et al, 2014). HCC tissues with low miR-744-5p had higher c-Myc protein expression (Lin et al, 2014).…”

“…Using luciferase reporter assays, it was demonstrated that miR-744-5p was able to suppress the HCC cell growth by targeting c-Myc (Lin et al, 2014). HCC tissues with low miR-744-5p had higher c-Myc protein expression (Lin et al, 2014). Prognosis The HCC cases with relative lower miR-744-5p expression level had higher recurrence rate after receiving liver transplantation.…”