Circular METRN RNA hsa_circ_0037251 Promotes Glioma Progression by Sponging miR-1229-3p and Regulating mTOR Expression
Circular METRN RNA hsa_circ_0037251 Promotes Glioma Progression by Sponging miR-1229-3p and Regulating mTOR Expression
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DOI：
10.1038/s41598-019-56417-8
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发表时间：
2019-12-24
影响因子：
4.6
通讯作者：
Zhang, Mingzhi
中科院分区：
文献类型：
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作者：
Cao, Qinchen;Shi, Yonggang;Zhang, Mingzhi
环状RNA（CircRNA）是近年来发现的一种存在于多种细胞过程和肿瘤中的非编码RNA。本研究旨在研究hsa_circ_0037251在胶质瘤进展中的作用，hsa_circ_0037251是由METRN基因的几个外显子产生的一种circRNA。通过体外实验发现hsa_circ_0037251的高表达与microRNA miR-1229- 3 p的低表达和mTOR的高表达有关。过表达hsa_circ_0037251促进胶质瘤细胞的增殖、侵袭和迁移，而敲低hsa_circ_00037251则促进胶质瘤细胞的凋亡并诱导G1期阻滞。然后，观察到hsa_circ_0037251直接海绵化miR-1229- 3 p，并且mTOR被鉴定为miR-1229- 3 p的直接靶标。此外，hsa_circ_0037251的敲低上调miR-1229- 3 p的表达，并抑制mTOR的表达。miR-1229- 3 p过表达或mTOR低表达可抑制胶质瘤细胞的生长。此外，即使使用siRNA敲低hsa_circ_00037251，用mTOR过表达载体转染也可以恢复胶质瘤细胞进展的能力。体内实验表明，hsa_circ_00037251促进了异种移植瘤的生长并缩短了存活期。这些结果表明hsa_circ_0037251可能通过hsa_circ_0037251/miR-1229- 3 p/mTOR轴作为肿瘤促进剂，并且这些潜在的生物标志物可能是胶质瘤的治疗靶点。
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.