title: Next generation sequencing analysis of miRNAs: MiR-127-3p inhibits glioblastoma proliferation and activates TGF-β signaling by targeting SKI.
abstract: Glioblastoma (GBM) proliferation is a multistep process during which the expression levels of many genes that control cell proliferation, cell death, and genetic stability are altered. MicroRNAs (miRNAs) are emerging as important modulators of cellular signaling, including cell proliferation in cancer. In this study, using next generation sequencing analysis of miRNAs, we found that miR-127-3p was downregulated in GBM tissues compared with normal brain tissues; we validated this result by RT-PCR. We further showed that DNA demethylation and histone deacetylase inhibition resulted in downregulation of miR-127-3p. We demonstrated that miR-127-3p overexpression inhibited GBM cell growth by inducing G1-phase arrest both in vitro and in vivo. We showed that miR-127-3p targeted SKI (v-ski sarcoma viral oncogene homolog [avian]), RGMA (RGM domain family, member A), ZWINT (ZW10 interactor, kinetochore protein), SERPINB9 (serpin peptidase inhibitor, clade B [ovalbumin], member 9), and SFRP1 (secreted frizzled-related protein 1). Finally, we found that miR-127-3p suppressed GBM cell growth by inhibiting tumor-promoting SKI and activating the tumor suppression effect of transforming growth factor-β (TGF-β) signaling. This study showed, for the first time, that miR-127-3p and its targeted gene SKI, play important roles in GBM and may serve as potential targets for GBM therapy.
authors: 1 Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang, China .
authors: Huawei
authors: H
authors: Jiang
authors: Chengmeng
authors: C
authors: Jin
authors: Jie
authors: J
authors: Liu
authors: Dasong
authors: D
authors: Hua
authors: Fan
authors: F
authors: Zhou
authors: Xiaoyan
authors: X
authors: Lou
authors: Na
authors: N
authors: Zhao
authors: Qing
authors: Q
authors: Lan
authors: Qiang
authors: Q
authors: Huang
authors: Jae-Geun
authors: JG
authors: Yoon
authors: Shu
authors: S
authors: Zheng
authors: Biaoyang
authors: B
authors: Lin
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C547276:MIRN127 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D016212:Transforming Growth Factor beta; C060614:SKI protein, human