MicroRNA-153-3p enhances cell radiosensitivity by targeting BCL2 in human glioma

Abstract

BackgroundGlioma is the most prevalent malignant tumor in human central nervous systems. Recently, the development of resistance to radiotherapy in glioma patients markedly vitiates the therapy outcome. MiR-153-3p has been reported to be closely correlated with tumor progression, but its effect and molecular mechanism underlying radioresistance remains unclear in glioma.MethodsThe expression of miR-153-3p was determined in radioresistant glioma clinical specimens as well as glioma cell lines exposed to irradiation (IR) using quantitative real-time PCR. Cell viability, proliferation and apoptosis were then evaluated by MTT assay, colony formation assay, Flow cytometry analysis and caspase-3 activity assay in glioma cells (U87 and U251). Tumor forming was evaluated by nude mice model in vivo. TUNEL staining was used to detect cell apoptosis in nude mice model. The target genes of miR-153-3p were predicted and validated using integrated bioinformatics analysis and a luciferase reporter assay.ResultsHere, we found that miR-153-3p was down-regulated in radioresistant glioma clinical specimens as well as glioma cell lines (U87 and U251) exposed to IR. Enhanced expression of miR-153-3p promoted the radiosensitivity, promoted apoptosis and elevated caspase-3 activity in glioma cells in vitro, as well as the radiosensitivity in U251 cell mouse xenografs in vivo. Mechanically, B cell lymphoma-2 gene (BCL2) was identified as the direct and functional target of miR-153-3p. Moreover, restoration of BCL2 expression reversed miR-153-3p-induced increase of radiosensitivity, apoptosis and caspase-3 activity in U251 cells in vitro. In addition, clinical data indicated that the expression of miR-153-3p was significantly negatively associated with BCL2 in radioresistance of glioma samples.ConclusionsOur findings suggest that miR-153-3p is a potential target to enhance the effect of radiosensitivity on glioma cells, thus representing a new potential therapeutic target for glioma.

miR‐15b enhances the proliferation and migration of lung adenocarcinoma by targeting BCL2

“…In several studies, BCL2 has been reported to act as a target gene of multiple miRNAs, including miR‐153, miR‐136 and miR‐365 . BCL2 has also been elucidated to be a target gene of miR‐15b in condylar hyperplasia and liver cancer .…”

miR‐16‐5p modulates the radiosensitivity of cervical cancer cells via regulating coactivator‐associated arginine methyltransferase 1

“…For example, miR‐365 enhances the sensitivity of non‐small cell lung cancer to radiation therapy by modulating cell division cycle 25A . MiR‐153‐3p enhances the radiosensitivity of human glioma cells by targeting B cell lymphoma‐2 . MiR‐199a‐3p promotes radioresistance in esophageal cancer by targeting adenylate kinase 4 .…”

“…MicroRNAs (miRNAs) are a class of small non‐coding RNAs containing 18–24 nucleotides that have post‐transcriptional regulation and result in translational inhibition or degradation by specific binding to the 3′‐untranslated region (3′‐UTR) of the target gene . Studies have reported that some miRNAs are involved in regulating the radiation response of different cancer cells to increase the sensitivity of radiotherapy or enhance the resistance of radiotherapy . For example, miR‐132 and miR‐18a enhance the sensitivity of CC radiotherapy, while miR‐208a increases the radioresistance of lung cancer cells, and miR‐106b induces radiotherapy resistance in colon cancer .…”

Non-Coding RNAs in Cancer Radiosensitivity: MicroRNAs and lncRNAs as Regulators of Radiation-Induced Signaling Pathways

“…This effect was modulated by Bcl-2 inhibition, since restoration of Bcl-2 expression reversed the miR-153-induced phenotype. Additionally, miR-153 enhanced the response to IR in xenograft mice [47]. Another pro-apoptotic miRNA, miR-193a, targeted Mcl-1.…”

“…We also present an overview of ncRNAs that alter radiosensitivity of cancer cells (Tables 1 and 2) and discuss the utilization of ncRNAs to improve the outcome of radiotherapy. [16,17] miR- 16 Cyclin D1 Cell cycle Prostate cancer [18] miR-18a ATM DSB repair Breast cancer, lung cancer * [19,20] HIF-1α -Lung cancer * [20] miR-22 SIRT1 Apoptosis Breast cancer [21] miR-23b ATG12 Autophagy Pancreatic cancer * [22] miR-24 H2AX DSB repair Leukemia [23] miR-26a ATM DSB repair Glioma [24] miR-26b DRAM1 Autophagy Breast cancer [25] miR-30a TP53INP1 Autophagy Prostate cancer [26] miR-33a HIF-1α Glycolysis Melanoma * [27] miR-34a LyGDI Apoptosis NSCLC [28] RAD51 DSB repair Lung cancer * [29] miR-99a mTOR Apoptosis NSCLC * [30] miR-100 ATM -Glioma [31] miR-101 DNA-PKcs -Glioma * [32] ATM -Glioma * [32] STMN1 Autophagy NPC [33] miR-107 RAD51 DSB repair Ovarian cancer [34] miR-124 CDK4 Apoptosis Glioma, ESCC [35,36] STAT3 Apoptosis NSCLC *, breast cancer [37,38] PIM 1 -Prostate cancer [39] miR-125a p21 -Cervical cancer [40] miR-125b c-Jun Apoptosis Breast cancer [41] miR-133a EGFR Apoptosis ESCC [42] miR-133b PKM2 Glycolysis NSCLC [43] miR-136 E2F1 Apoptosis Cervical cancer [44] [45] miR-144 PIM 1 -Prostate cancer [39] miR-150 AKT Apoptosis NK/T cell lymphoma * [46] miR-153 Bcl-2 Apoptosis Glioma * [47] miR-155 RAD51 DSB repair Triple negative breast cancer *…”