MicroRNA-519d-3p inhibits cell proliferation and cell cycle G1/S transition in glioma by targeting CCND1

Abstract

Glioma is the most common highly malignant primary brain tumor. MicroRNA-519d-3p exerts important effects in several tumors, but its functional role in glioma remained poorly understood. In this study, we found miR-519d-3p expression was significantly decreased in glioma tissues and cell lines. Moreover, the in vitro experiments showed that overexpression of miR-519d-3p suppressed cell proliferation and induced cell cycle G0/G1 phase arrest using MTT and flow cytometry assays in glioma cell lines, U87 and U251. Mechanistically, Cyclin D1 (CCND1) was predicted and confirmed as the direct target genes of miR-519d-3p using luciferase report assay. In addition, knockdown of CCND1 imitated the suppressive effects of miR-519d-3p on cell proliferation and cell cycle progression. Furthermore, restoration of CCND1 reversed the effects of miR-519d-3p overexpression in glioma cells. Taken together, these data demonstrate that suppression of CCND1 by miR-519d-3p might be a therapeutic target for glioma. Abbreviations miR-519d-3p: microRNA-519d-3p; CCND1: Cyclin D1; ATCC: American Type Culture Collection; MTT: 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide; PI: propidium iodide; WT: wild type; MUT: mutant type; SD: standard deviation

<p>miR-519d-3p Overexpression Inhibits P38 and PI3K/AKT Pathway via Targeting VEGFA to Attenuate the Malignant Biological Behavior of Non-Small Cell Lung Cancer</p>

“…The regulation of mir-519d-3p is considered to be a potential strategy for the treatment of a variety of cancers. Ma and Li 25 reported that miR-519d-3p expression was significantly reduced in glioma cell lines and tissues, while overexpression of miR-519d-3p inhibited cell proliferation and induced cell cycle G0/G1 arrest. Liang et al 26 reported that miR-591d-3p expressed lowly in pancreatic cancer cell lines and tissues, and overexpression of miR-519d-3p significantly inhibited the proliferation of pancreatic cancer cells and Wnt/β-catenin signaling via targeting RPS15A.…”

The overexpression of miRNA-212-5p inhibited the malignant proliferation of liver cancer cells HepG2 and the tumor formation in nude mice with transplanted tumor through down-regulating SOCS5

“…The higher the PNCA index, the faster the cell division and proliferation, which may promote the ability of the cell to obtain unlimited proliferation and eventually change the morphological structure and function of the cell ( 27 ). Ma and Li ( 28 ) found that the up-regulation of hsa-miR-212-5p expression can inhibit the proliferation and invasion of melanoma WM35 and A375 cells. This study found that the targeting inhibition of SOCS5 by miR-212-5p overexpression could reduce the protein expression levels of Ki67 and PCNA in HepG2 cells and decrease the Ki67 positive expression rate in nude mice.…”

miR‑519d‑3p/HIF‑2α axis increases the chemosensitivity of human cervical cancer cells to cisplatin via inactivation of PI3K/AKT signaling

“…However, evidence on the role of miR-519d-3p in cervical cancer DDP resistance is limited. Previous studies have demonstrated that miR-519d-3p functions as a tumor suppressor in several tumors (11)(12)(13). In gastric cancer, miR-519d-3p suppresses cell proliferation and invasion by downregulating B-cell lymphoma 6 (11).…”

“…Previous studies have revealed that miRNAs have a number of roles such as regulating the cell cycle, cell proliferation, migration, invasion, adhesion, angiopoiesis and apoptosis, as well as having an important role in cervical cancer occurrence and progression (9,10). Recent studies have shown that miR-519-3p regulates cell proliferation, migration and invasion in multiple cancer cells (11)(12)(13). The authors' previous study revealed that in cervical cancer, under hypoxic conditions miR-519d-3p plays an important role in the regulation of HIF-2α expression (14).…”