MicroRNA-490-5P Targets CCND1 to Suppress Cellular Proliferation in Glioma Cells and Tissue Through Cell Cycle Arrest.

Abstract

Glioma is a type of tumor that starts in the glial cells of brain and spine. However, the underlying molecular mechanisms of miRNAs dysregulation in glioma initiation and progression is largely unclear. To further understand the molecular mechanism of miR-490-5P functions and how miR-490 regulated CCND1 function. The expression of miR-490-5P in glioma tissues and cells was measured by qRT-PCR and ISH. Cell transfection is responsible for miR-490-5P overexpression and knockdown. CCK-8 and clone formation assay are applicable to examine the capacity of glioma cells proliferation. Cell cycle analysis is used to test glioma cells cycle distribution with miR-490-5P overexpression or downregulation. Further, in vivo tumor exnograft studies are used to examine the effects of miR- 490-5P on glioma malignancy in vivo. We found overexpression of miR-490 lead to glioma cells cycle arrest at G1 phase and decreased proliferation. Next-step functional assays showed miR-490 regulated CCND1 expression and manipulated giloma cells proliferation. Finally, negative regulation of miR-490 in CCND1 function was validated through in vivo nude mice tumorigenesis assay and IHC examination in glioma tissue. Overall, these results showed that epigenetic regulation of CCND1 via miR-490 was essential to glioma and provide a new insight into glioma diagnosis, treatment, prognosis and further translational investigations.