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

Abstract

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 up-regulated 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.

CircRNA PIP5K1A promotes the progression of glioma through upregulation of the TCF12/PI3K/AKT pathway by sponging miR-515-5p

“…Meanwhile, circ-0006948 enhances HMGA2 expression by sponging miR-490-3p, thus inducing EMT and aggravating ESCC [ 6 ]. In addition, circ-0037251 affects glioma cell proliferation and metastasis by regulating the miR-1229-3p/mTOR axis [ 7 ]. CircPIP5K1A is a newly discovered cancer-related circRNA, which is a powerful regulator in tumors.…”

circHIPK3 Acts as Competing Endogenous RNA and Promotes Non-Small-Cell Lung Cancer Progression through the miR-107/BDNF Signaling Pathway

“…The most common function of circRNAs is to act as miRNA sponges in the regulation of the cell signaling pathway. For example, Cao et al found that hsa_circ_0037251 enhanced the progression of glioma via sponging miR-1229-3p [ 9 ]. Moreover, circRNAs can also engage in other cell activities.…”

Circular RNAs: Emerging Role in Cancer Diagnostics and Therapeutics

“…Overexpression of circSMARCA5 inhibits the proliferation and migration of HCC cells (Li Z. et al, 2019). CircPTGR1 promoted HCC progression via the miR-449a/MET pathway and its knockdown reduced HCC progression Wang G. et al, 2019). CircRHOT1 facilitated HCC progression by recruiting TIP60, a histone acetyltransferase to the nuclear orphan receptor NR2F6 promoter to enhance its expression (Wang L. et al, 2019).…”

“…Downregulation of cZNF292 reduced proliferation in GBM cells and suppressed human glioma tube formation by modulating Wnt/β-catenin signaling pathway (Yang P. et al, 2019). Circ_0037251 enhances GBM progression by sponging miR-1229-3p and upregulating mTOR (Cao et al, 2019). Knockdown of circ_0037251 inhibited the expression of mTOR leading to increased apoptosis and promoting cell-cycle arrest (Cao et al, 2019).…”

“…Circ_0037251 enhances GBM progression by sponging miR-1229-3p and upregulating mTOR (Cao et al, 2019). Knockdown of circ_0037251 inhibited the expression of mTOR leading to increased apoptosis and promoting cell-cycle arrest (Cao et al, 2019). CircMAPK4 functions as an oncogene to enhance GBM cell survival by sponging miR-125a-3p and regulating the p38/MAPK pathway, its downregulation induces apoptosis of GBM cells (He et al, 2020a).…”