PMID- 31609809 OWN - NLM STAT- MEDLINE DCOM- 20210614 LR - 20210614 IS - 1473-5709 (Electronic) IS - 0959-8278 (Linking) VI - 29 IP - 2 DP - 2020 Mar TI - Circular RNA Pleiotrophin promotes carcinogenesis in glioma via regulation of microRNA-122/SRY-box transcription factor 6 axis. PG - 165-173 LID - 10.1097/CEJ.0000000000000535 [doi] AB - BACKGROUND: Circular RNAs (circRNAs) are recently identified as gene regulators in mammals and play important roles in carcinogenesis of cancer. For example, circRNA_PTN has been recognized as a biomarker of human cancer and is overexpressed in glioma. The molecular function of circRNA_PTN and its downstream targets in glioma, however, remains elusive. METHODS: Quantitative polymerase chain reaction analysis was used to measure the expression of circular RNA pleiotrophin (circ_PTN) and miR-122. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, propidium iodide and Annexin-V/propidium iodide assay were performed to determine cell proliferation and apoptosis of glioma cells. Circular RNA Interactome and TargetScan were used to predict the potential microRNA targeting of circ_PTN and the potential targets of miR-122, respectively. Luciferase activity assay was used to validate these interactions. Downstream molecular mechanisms, including SRY-box transcription factor 6 (SOX6), extracellular regulated protein kinases (ERK), Cyclin D1, B-cell lymphoma-2 (BCL-2) and BCL2 associated X, apoptosis regulator (BAX), were determined by western blot. RESULTS: Circ_PTN was overexpressed in glioma cells, and its knockdown induced cell proliferation inhibition, cell cycle arrest and apoptosis in glioma cells. The target microRNA of circ_PTN was predicted to be miR-122, the expression of which was negatively correlated with circ_PTN in glioma cells. Moreover, SOX6 was predicted as a potential target of miR-122, and miR-122 overexpression decreased SOX6 expression. MiR-122 inhibitor reversed the tumor-suppressing effects of circ_PTN knockdown, while overexpression of SOX6 impaired the miR-122 overexpression-induced cell growth inhibition and apoptosis. In addition, mitogen activated kinase-like protein (MAPK)/ERK pathway was involved in circ_PTN/miR-122/SOX6 axis. CONCLUSIONS: Circ_PTN acted as a sponge of miR-122 and upregulated miR-122 target SOX6, thus promoting carcinogenesis of glioma cells. FAU - Chen, Chen AU - Chen C AD - Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou. AD - Department of Neurosurgery, Yancheng City No. 1 People's Hospital, Yancheng. FAU - Deng, Lu AU - Deng L AD - Department of Orthopedics, Yancheng City No. 1 People's Hospital, Yancheng, P.R. China. FAU - Nie, De-Kang AU - Nie DK AD - Department of Neurosurgery, Yancheng City No. 1 People's Hospital, Yancheng. FAU - Jia, Feng AU - Jia F AD - Department of Neurosurgery, Yancheng City No. 1 People's Hospital, Yancheng. FAU - Fu, Lin-Shan AU - Fu LS AD - Department of Neurosurgery, Yancheng City No. 1 People's Hospital, Yancheng. FAU - Wan, Zheng-Qiang AU - Wan ZQ AD - Department of Neurosurgery, Yancheng City No. 1 People's Hospital, Yancheng. FAU - Lan, Qing AU - Lan Q AD - Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Eur J Cancer Prev JT - European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) JID - 9300837 RN - 0 (Carrier Proteins) RN - 0 (Cytokines) RN - 0 (MIRN122 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Circular) RN - 0 (SOX6 protein, human) RN - 0 (SOXD Transcription Factors) RN - 134034-50-7 (pleiotrophin) SB - IM MH - Apoptosis/genetics MH - Brain Neoplasms/*genetics/pathology MH - Carcinogenesis/genetics MH - Carrier Proteins/genetics MH - Cell Line, Tumor MH - Cell Proliferation/genetics MH - Cytokines/genetics MH - Gene Expression Regulation, Neoplastic MH - Gene Knockdown Techniques MH - Glioma/*genetics/pathology MH - Humans MH - MAP Kinase Signaling System/genetics MH - MicroRNAs/*metabolism MH - RNA, Circular/genetics/*metabolism MH - SOXD Transcription Factors/*genetics EDAT- 2019/10/15 06:00 MHDA- 2021/06/16 06:00 CRDT- 2019/10/15 06:00 PHST- 2019/10/15 06:00 [pubmed] PHST- 2021/06/16 06:00 [medline] PHST- 2019/10/15 06:00 [entrez] AID - 00008469-202003000-00010 [pii] AID - 10.1097/CEJ.0000000000000535 [doi] PST - ppublish SO - Eur J Cancer Prev. 2020 Mar;29(2):165-173. doi: 10.1097/CEJ.0000000000000535.