Circular METRN RNA hsa_circ_0037251 Promotes Glioma Progression by Sponging miR-1229-3p and Regulating mTOR Expression

被引:26
|
作者
Cao, Qinchen [1 ]
Shi, Yonggang [1 ]
Wang, Xinxin [2 ]
Yang, Jing [1 ]
Mi, Yin [1 ]
Zhai, Guan [3 ]
Zhang, Mingzhi [4 ]
机构
[1] Zhengzhou Univ, Affiliated Hosp 1, Dept Radiat Therapy, Zhengzhou 450052, Peoples R China
[2] Zhengzhou Univ, Affiliated Hosp 1, Dept Neurol, Zhengzhou 450052, Peoples R China
[3] Zhengzhou Univ, Affiliated Hosp 1, Dept Neurosurg, Zhengzhou 450052, Peoples R China
[4] Zhengzhou Univ, Affiliated Hosp 1, Dept Oncol, Zhengzhou 450052, Peoples R China
关键词
UNITED-STATES; PRIMARY BRAIN; ABUNDANT; GROWTH; CANCER; TUMORS;
D O I
10.1038/s41598-019-56417-8
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Circular RNAs (circRNAs) are a newly identifed non-coding RNA in many cellular processes and tumours. This study aimed to investigate the role of hsa_circ_0037251, one circRNA generated from several exons of the gene termed METRN, in glioma progression. Through in vitro experiments, we discovered that high expression of hsa_circ_0037251 was related to low expression of the microRNA miR-1229-3p and high expression of mTOR. The over-expressed hsa_circ_0037251 promoted cell proliferation, invasion and migration in glioma, while knockdown of hsa_circ_00037251 promoted cell apoptosis and induced G1 phase arrest. Then, hsa_circ_0037251 was observed to directly sponge miR-1229-3p, and mTOR was identified as a direct target of miR-1229-3p. In addition, knockdown of hsa_circ_0037251 upregulated the expression of miR-1229-3p and inhibited the expression of mTOR. And overexpression of miR-1229-3p or low-expressed mTOR inhibited the glioma cell progression. Furthermore, transfection with mTOR overexpression vectors can restore the abilities of glioma cell progression even if hsa_circ_00037251 was knocked down using siRNAs. In vivo experiments revealed that hsa_circ_00037251 promoted the growth of xenografted tumours and shortened the survival period. These results indicated that hsa_circ_0037251 may act as a tumour promoter by a hsa_circ_0037251/miR-1229-3p/mTOR axis, and these potential biomarkers may be therapeutic targets for glioma.
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页数:10
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