PMID- 29218086 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 1943-8141 (Print) IS - 1943-8141 (Electronic) IS - 1943-8141 (Linking) VI - 9 IP - 11 DP - 2017 TI - MicroRNA-520d-5p inhibits human glioma cell proliferation and induces cell cycle arrest by directly targeting PTTG1. PG - 4872-4887 AB - Glioma accounts for the majority of primary malignant brain tumors in adults and is highly aggressive. Although various therapeutic approaches have been applied, outcomes of glioma treatment remain poor. Acquiring a better understanding of the pathogenic mechanisms is essential to the design of effective therapeutic strategies. Previous studies have found that miR-520d-5p was negatively correlated with glioma grade, but its role and mechanism in glioma progression remain largely unknown. In the present study, we reported that miR-520d-5p directly targeted the Pituitary Tumor Transforming Gene 1 (PTTG1) and functioned as a tumor-suppressor in glioma. The expression of miR-520d-5p in glioma cells and specimens were detected by Quantitative reverse transcription-PCR and Fluorescence in situ hybridization (FISH). The effects of miR-520d-5p on glioma progression was examined by cell-counting kit 8, colony formation, 5-ethynyl-2-deoxyuridine (EDU) and flow cytometry assays. Using bioinformatics and luciferase reporter assays, we identified PTTG1 as a novel and direct target of miR-520d-3p. A xenograft model was used to study the effect of miR-520d-5p on tumor growth and angiogenesis. We found that miR-520d-5p expression was significantly decreased in glioma cell lines and tissues. Overexpression of miR-520d-5p showed a significant inhibitory effect on cell proliferation and accompanied cell cycle G0/G1 arrest in U87-MG and LN229 glioma cells. PTTG1 was a novel and direct target of miR-520d-5p, and the protein expression of PTTG1 was markedly reduced after overexpression of miR-520d-5p in U87-MG and LN229 cells. Overexpression of PTTG1 reversed the inhibitory effect of miR-520d-5p on glioma cell proliferation. In vivo studies confirmed that miR-520d-5p overexpression retarded the growth of U87 xenograft tumors, which was accompanied by reduced expression of PTTG1. In conclusion, these results provide compelling evidence that miR-520d-5p functions as an anti-onco-miRNA, which is important in inhibiting cell proliferation in GBM, and its anti-oncogenic effects are mediated chiefly through direct suppression of PTTG1 expression. Therefore, we suggest that miR-520d-5p is a potential candidate for the prevention of glioblastoma. FAU - Zhi, Tongle AU - Zhi T AD - Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029, Jiangsu Province, China. FAU - Jiang, Kuan AU - Jiang K AD - Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029, Jiangsu Province, China. AD - Department of Neurosurgery, Yixing People's HospitalYixing 214200, Jiangsu Province, China. FAU - Xu, Xiupeng AU - Xu X AD - Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029, Jiangsu Province, China. FAU - Yu, Tianfu AU - Yu T AD - Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029, Jiangsu Province, China. FAU - Wu, Weining AU - Wu W AD - Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029, Jiangsu Province, China. FAU - Nie, Er AU - Nie E AD - Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029, Jiangsu Province, China. FAU - Zhou, Xu AU - Zhou X AD - Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029, Jiangsu Province, China. FAU - Jin, Xin AU - Jin X AD - Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029, Jiangsu Province, China. FAU - Zhang, Junxia AU - Zhang J AD - Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029, Jiangsu Province, China. FAU - Wang, Yingyi AU - Wang Y AD - Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029, Jiangsu Province, China. FAU - Liu, Ning AU - Liu N AD - Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029, Jiangsu Province, China. LA - eng PT - Journal Article DEP - 20171115 PL - United States TA - Am J Transl Res JT - American journal of translational research JID - 101493030 PMC - PMC5714772 OTO - NOTNLM OT - PTTG1 OT - glioma OT - miR-520d-5p OT - proliferation COIS- None. EDAT- 2017/12/09 06:00 MHDA- 2017/12/09 06:01 PMCR- 2017/11/15 CRDT- 2017/12/09 06:00 PHST- 2017/08/01 00:00 [received] PHST- 2017/10/10 00:00 [accepted] PHST- 2017/12/09 06:00 [entrez] PHST- 2017/12/09 06:00 [pubmed] PHST- 2017/12/09 06:01 [medline] PHST- 2017/11/15 00:00 [pmc-release] PST - epublish SO - Am J Transl Res. 2017 Nov 15;9(11):4872-4887. eCollection 2017.