miR‑138‑5p suppresses glioblastoma cell viability and leads to cell cycle arrest by targeting cyclin D3

Abstract

Although malignant glioblastoma (GBM) treatment has significantly improved in the past few decades, the prognosis of GBM remains unsatisfactory. MicroRNA (miR)-138-5p has been reported as a tumor suppressor in several types of human cancer; however, little is known about the function of miR-138-5p in GBM. The present study aimed to investigate the role of miR-138-5p in GBM as well as the underlying molecular mechanisms. The present study performed bioinformatics analysis, reverse transcription-quantitative (RT-q)PCR, western blotting, cell viability assays, colony formation assays, invasion assays and cell cycle analysis to investigate the biological function of miR-138-5p in both patient tissues and cell lines. In addition, miR-138-5p targets in GBM were predicted using Gene Expression Omnibus website and further validated by a dual luciferase reporter gene assay. The results revealed that miR-138-5p expression levels in patients with GBM from a Gene Expression Omnibus dataset were significantly downregulated. RT-qPCR analysis of miR-138-5p expression levels also revealed similar results in GBM tissues and cell lines. The upregulation of miR-138-5p expression levels using a mimic significantly inhibited the cell viability, colony formation and the G 0 /G 1 to S progression in GBM cell lines, suggesting that miR-138-5p may be a tumor suppressor. Moreover, miR-138-5p was discovered to directly target cyclin D3 (CCND3), a protein that serves an important role in the cell cycle, and inhibited its expression. Finally, silencing CCND3 using small interfering RNA suppressed the viability of GBM cells. In conclusion, the results of the present study suggested that miR-138-5p may function as a tumor suppressor in GBM by targeting CCND3, indicating that miR-138-5p may be a novel therapeutic target for patients with GBM.

Modulating glioblastoma chemotherapy response: Evaluating long non-coding RNA effects on DNA damage response, glioma stem cell function, and hypoxic processes

“… 25 Linc00174 has been reported to strengthen TMZ resistance in GBM cells by directly targeting miR-138-5p , a tumor suppressive miRNA shown to arrest GBM cell cycle. 69 By inhibiting miR-138-5p , linc00174 increases SRY-Box Transcription Factor 9 (SOX9), a downstream target of miR-138-5p . In gliomas, SOX9 has been shown to maintain the self-renewal ability of GSCs.…”

Non‐coding RNA‐associated competitive endogenous RNA regulatory networks: Novel diagnostic and therapeutic opportunities for hepatocellular carcinoma

“… 153 miR‐138‐5 has been reported to act as a tumour suppressor in several types of human cancers. 154 The function and molecular mechanism of circC16orf62 have been investigated in HCC. CircC16orf62 has been shown to be significantly up‐regulated in HCC.…”

“…AKT pathway plays an important role in the regulation of several processes involved in the development and progression of HCC; such as controlling growth, proliferation and survival of tumour cells 153 . miR‐138‐5 has been reported to act as a tumour suppressor in several types of human cancers 154 . The function and molecular mechanism of circC16orf62 have been investigated in HCC.…”

Network Analysis Identifies Drug Targets and Small Molecules to Modulate Apoptosis Resistant Cancers

“…miR-492 is known to enhance tumor growth inhibition in colorectal cancer [ 38 ]. hsa-miR-138-5p (up) regulating IKBKB in GBM ( Figure S7B ), is reported to suppress tumor development in GBM [ 39 ]. We observed that hsa-miR-181a-5p (up) connected to RHOA in GBM and SCLC ( Figure S7B ) is known to regulate the cell growth pathways in tumors [ 40 ].…”