MiR-4521 plays a tumor repressive role in growth and metastasis of hepatocarcinoma cells by suppressing phosphorylation of FAK/AKT pathway via targeting FAM129A

MiR-4521 plays a tumor repressive role in growth and metastasis of hepatocarcinoma cells by suppressing phosphorylation of FAK/AKT pathway via targeting FAM129A

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Introduction: Globally, hepatocellular carcinoma (HCC) is the sixth most common malignancy and it has the fourth highest mortality.MicroRNAs play a significant part in biological processes in cell formation and advancement by targeting genes in many cancers including HCC.Objective: In the present study we examine the involvement of miR-4521 and FAM129A correlations in HCC occurrence and progression.Methods: Expression levels of miR-4521 and FAM129A in HCC tissues and cells were detected.

Immunohistochemistry was carried out to detect expression of FAM129A, MMP9 and TIMP-1 in HCC tissues.Western blot assays were used to examine expression levels of different genes involve in signaling pathways.Transwell chamber, MTT 5-HTP 100 and wound healing assays were performed to check cell migration, invasion and proliferation rates.Results: Overexpression of FAM129A positively correlated with upregulation of MMP9 and negatively correlated with TIMP-1 in HCC patient samples, which encouraged progression and metastasis of HCC.

An antagonistic relation between miR-4521 and FAM129A was detected in current study, down-regulation of miR-4521 and up-regulation of FAM129A was demonstrated in HCC tissues and cell lines as compare to normal tissue samples and the normal cell line LO2.Overexpressing miR-4521 and silencing FAM129A impaired HCC cell migratory and invasive properties and suppressed cell proliferation.Mutually, miR-4521-FAM129A axial regulation inhibited in vitro proliferation of cells by promoting apoptosis through the p-FAK/p-AKT/MDM2/P53 and p-FAK/p-AKT/BCL-2/BAX/Cytochrome-C/Caspase-3/Caspase-9 pathways, respectively, and suppressed the migration and invasion capabilities of HCCLM3 and HepG2 cells via the TIMP-1/MMP9/MMP2 and p-FAK/p-AKT pathway.Conclusion: Our work found the axial regulation mechanism of miR-4521-FAM129A in HCC.

Deficiency of miR-4521 and abundance of FAM129A synergistically enhanced cancer progression by increasing cell proliferation and malignant invasion and by inhibiting apoptosis.These discoveries BCAA SPLASH BLUE RASPBERRY suggest that miR-4521/FAM129A might play a vital role in hepatic cancer progression and could be a candidate for its therapy.