Circular RNA Pleiotrophin promotes carcinogenesis in glioma via regulation of microRNA-122/SRY-box transcription factor 6 axis

被引:17
作者
Chen, Chen [1 ,2 ]
Deng, Lu [3 ]
Nie, De-Kang [2 ]
Jia, Feng [2 ]
Fu, Lin-Shan [2 ]
Wan, Zheng-Qiang [2 ]
Lan, Qing [1 ]
机构
[1] Soochow Univ, Dept Neurosurg, Affiliated Hosp 2, 1055 Sanxiang Rd, Suzhou 215004, Jiangsu, Peoples R China
[2] Yancheng City 1 Peoples Hosp, Dept Neurosurg, Yancheng, Peoples R China
[3] Yancheng City 1 Peoples Hosp, Dept Orthoped, Yancheng, Peoples R China
关键词
Circular RNA Pleiotrophin; extracellular regulated protein kinases; glioma; microRNA-122; SRY-box transcription factor 6; EXPRESSION; MIR-122; SOX6; IDENTIFICATION; CARCINOMA; APOPTOSIS; PROTEINS; MICRORNA; SURVIVAL; PATHWAY;
D O I
10.1097/CEJ.0000000000000535
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:165 / 173
页数:9
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