IADR Abstract Archives
miR-372 targets p62 and enhances the progression of oral carcinoma
Objectives: Oral squamous cell carcinoma (OSCC) is one of the prevalent neoplasms worldwide. miRNAs are involved in the pathogenesis of various human malignancies, functioning by post-transcriptional down-regulation of target genes. miR-372 is known to be highly expressed in OSCC tissues and other malignancies. The purpose of this study is to discovers the novel target of miR-372 and its modulation in OSCC.
Methods: Using in silico prediction modules, qRT-PCR analysis, Western blot analysis, reporter assays and exogenous expression constructs, this study discovers that p62 is a novel target of miR-372 in OSCC.
Results: Exogenous miR-372 expression and knockdown of p62 both enhance the migration of OSCC cells, but do not affect OSCC cell proliferation. p62 is able to induce the expression of NADPH quinone oxidoreductase 1, which results in an attenuation of reactive oxygen species (ROS) and reduced OSCC cell migration. Hypoxia associated p62 down-regulation could be mediated by miR-372 expression and targeting, which is independent from autophagy induction.
Conclusions: The regulation of miR-372 on p62 is contributive to the increased OSCC cell migration in hypoxic microenvironment. A correlation between the higher miR-372 expression and lower p62 expression is found in OSCC tissues. Furthermore, we demonstrate that the plasma level of miR-372 in OSCC patients is significantly increased as the tumors advance. This study concludes that miR-372 expression modulates OSCC progression by targeting p62, which then disrupts ROS homeostasis and motility in tumor cells.
Methods: Using in silico prediction modules, qRT-PCR analysis, Western blot analysis, reporter assays and exogenous expression constructs, this study discovers that p62 is a novel target of miR-372 in OSCC.
Results: Exogenous miR-372 expression and knockdown of p62 both enhance the migration of OSCC cells, but do not affect OSCC cell proliferation. p62 is able to induce the expression of NADPH quinone oxidoreductase 1, which results in an attenuation of reactive oxygen species (ROS) and reduced OSCC cell migration. Hypoxia associated p62 down-regulation could be mediated by miR-372 expression and targeting, which is independent from autophagy induction.
Conclusions: The regulation of miR-372 on p62 is contributive to the increased OSCC cell migration in hypoxic microenvironment. A correlation between the higher miR-372 expression and lower p62 expression is found in OSCC tissues. Furthermore, we demonstrate that the plasma level of miR-372 in OSCC patients is significantly increased as the tumors advance. This study concludes that miR-372 expression modulates OSCC progression by targeting p62, which then disrupts ROS homeostasis and motility in tumor cells.