MicroRNA-30e-3p inhibits glioma development and promotes drug sensitivity to temozolomide treatment via targeting canopy FGF signaling regulator 2
- 17 October 2021
- journal article
- research article
- Published by Taylor & Francis Ltd in Cell Cycle
- Vol. 20 (22), 2361-2371
- https://doi.org/10.1080/15384101.2021.1974789
Abstract
Glioma is one of the most aggressive malignancies in the central nervous system and the prognosis of glioma patients remains poor. In this study, we investigated the function of microRNA-30e-3p (miR-30e-3p) in glioma development and its regulatory role in drug-resistance to temozolomide (TMZ). We found that miR-30e-3p was downregulated in glioma tissues and cell lines. Ectopic expression of miR-30e-3p inhibited the growth of glioma cells and arrested cell cycle at G0/G1 phase. Canopy FGF signaling regulator 2 (CNPY2) was predicted as a direct target of miR-30e-3p by bioinformatics analysis. Luciferase reporter assay confirmed the interaction between miR-30e-3p and CNPY2. We also demonstrated that miR-30e-3p suppressed glioma xenograft tumor development invivo and the inhibition was abolished by CNPY2 overexpression. In addition, we showed that overexpression of miR-30e-3p enhanced the sensitivity of glioma cell to TMZ treatment. Glioma cells with miR-30e-3p overexpression had decreased cell proliferation and enhanced cell apoptosis upon TMZ treatment. Moreover, we revealed that miR-30e-3p modulated TMZ sensitivity of glioma cells via negatively regulating CNPY2. Taken together, our findings demonstrate that miR-30e-3p plays a critical role in glioma development and drug sensitivity to TMZ treatment via negatively regulating CNPY2 expression. The study suggests that miR-30e-3p/CNPY2 could be developed as a novel target to improve the glioma therapy. Abbreviations: miR-30e-3p, microRNA-30e-3p; TMZ, temozolomide; CNPY2, canopy FGF signaling regulator 2; 3ʹ-UTR, 3ʹ untranslated region; NC, negative control.Keywords
This publication has 26 references indexed in Scilit:
- The role of MicroRNAs in human cancerSignal Transduction and Targeted Therapy, 2016
- Role of MicroRNAs in Malignant GliomaChinese Medical Journal, 2015
- A secreted protein (Canopy 2, CNPY2) enhances angiogenesis and promotes smooth muscle cell migration and proliferationCardiovascular Research, 2015
- Unravelling tumour heterogeneity—implications for therapyNature Reviews Clinical Oncology, 2015
- Expression of CNPY2 in Mouse Tissues: Quantification and LocalizationPLOS ONE, 2014
- MicroRNA Expression Signatures Determine Prognosis and Survival in Glioblastoma Multiforme—a Systematic OverviewMolecular Neurobiology, 2014
- Multiple-to-Multiple Relationships between MicroRNAs and Target Genes in Gastric CancerPLOS ONE, 2013
- Emerging role of microRNA-27a in human malignant glioma cell survival via targeting of prohibitinMolecular Medicine Reports, 2012
- Acquired Resistance to Temozolomide in Glioma Cell Lines: Molecular Mechanisms and Potential Translational ApplicationsOncology, 2010
- MicroRNAs: Target Recognition and Regulatory FunctionsCell, 2009