title: miR-423-5p knockdown enhances the sensitivity of glioma stem cells to apigenin through the mitochondrial pathway.
abstract: This study aimed to investigate the effect of miR-423-5p on the sensitivity of glioma stem cells to apigenin and to explore the potential mechanism. Previous research indicated that apigenin can effectively inhibit the proliferation of many cancer cells, including glioma cells, though our data unexpectedly showed that apigenin had no effect on glioma stem cell apoptosis. As many studies have reported that malignant transformation and progression of glioma are due to glioma stem cells, an anti-glioma stem cell approach has become an important direction for glioma treatment. In this study, we found miR-423-5p to be overexpressed in glioma tissues and corresponding glioma stem cells. Downregulation of miR-423-5p repressed glioma stem cell growth but did not cause apoptosis. Based on the concept of "Pharmaco-miR," this study further demonstrated that the combination of miR-423-5p knockdown and apigenin had a notable additive effect on inhibiting proliferation and promoting apoptosis in glioma stem cells. Hoechst staining showed higher apoptosis rates and typical apoptotic morphological changes of the cell nucleus, and JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimi-dazolylcarbocya-nine iodide) staining revealed reduced mitochondrial membrane potential. Further research demonstrated that the mechanism is associated with a shift in the Bax/Bcl-2 ratio, an increased cytochrome c level, Apaf-1 induction, and caspase-3 activation. In conclusion, this study indicates that downregulation of miR-423-5p enhances the sensitivity of glioma stem cells to apigenin through the mitochondrial pathway.
authors.affiliation: Department of Neurosurgery, Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, Suzhou, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Department of Neurosurgery, Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, Suzhou, P.R. China.
authors.forename: Xifeng
authors.initials: X
authors.lastname: Fei
authors.affiliation: Department of Neurosurgery, Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, Suzhou, P.R. China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, Suzhou, P.R. China.
authors.forename: Dongyi
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, Suzhou, P.R. China.
authors.forename: Hanchun
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, Suzhou, P.R. China.
authors.forename: Mian
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, Suzhou, P.R. China.
authors.forename: Shijun
authors.initials: S
authors.lastname: Zhou
mesh_terms: D047310:Apigenin / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects* / Q000502:physiology; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000502:physiology*; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology
chemical_list: C548900:MIRN423 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D047310:Apigenin; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: apigenin; apoptosis; glioma stem cells; miR-423-5p; mitochondrial