MicroRNA-361-5p slows down gliomas development through regulating UBR5 to elevate ATMIN protein expression

Abstract

MicroRNA (miR)-361-5p has been studied to suppress gliomas development. Based on that, an insight into the regulatory mechanism of miR-361-5p in gliomas was supplemented from ubiquitin protein ligase E3 component N-recognin 5 (UBR5)-mediated ubiquitination of ataxia-telangiectasia mutated interactor (ATMIN). miR-361-5p, ATMIN, and UBR5 levels were clinically analyzed in gliomas tissues, which were further validated in gliomas cell lines. Loss/gain-of-function method was applied to determine the roles of miR-361-5p and UBR5 in gliomas, as to cell viability, migration, invasion, colony formation ability, and apoptosis in vitro and tumorigenesis in vivo. The relationship between miR-361-5p and UBR5 was verified and the interaction between UBR5 and ATMIN was explored. It was detected that reduced miR-361-5p and ATMIN and enhanced UBR5 levels showed in gliomas. Elevating miR-361-5p was repressive in gliomas progression. UBR5 was directly targeted by miR-361-5p. UBR5 can ubiquitinate ATMIN. miR-361-5p suppressed gliomas by regulating UBR5-mediated ubiquitination of ATMIN. Downregulating UBR5 impeded gliomas tumor growth in vivo. Upregulating miR-361-5p targets UBR5 to promote ATMIN protein expression, thus to recline the malignant phenotype of gliomas cells.

Transcriptome Sequencing Reveals Tgf-β-Mediated Noncoding RNA Regulatory Mechanisms Involved in DNA Damage in the 661W Photoreceptor Cell Line

“…Most importantly, our study indicated that Gm20559 / miR-361-5p could stabilize/impair DNA stability in PRs, respectively ( Figure 5 A–F), which is indirectly supported by previous studies. For example, it was demonstrated that miR-361-5p was associated with PARP1, ubiquitin protein ligase E3 component N-recognin 5 (UBR5) and ataxia-telangiectasia mutated interactor (ATMIN) in tumors, which are enriched in DNA damage and repair [ 47 , 48 ]. Of note is the fact that miR-361-5p upregulation could reduce UBR5 expression [ 47 ], therefore inhibiting ATMIN ubiquitination, attenuating the restoration of ATM and impairing DNA repair [ 49 ].…”

LncRNA MDRL Mitigates Atherosclerosis through miR-361/SQSTM1/NLRP3 Signaling

“…Previous studies demonstrated that miR-361 functioned as a regulator in glioma aerobic glycolysis and proliferation [ 25 ]. In addition, systematic delivery of miR-361 impeded glioma development through suppressing UBR5 [ 26 ]. In contrast with these phenomena, our study showed that effective delivery of miR-361 partly offset the protective effect of MDRL on the development of atherosclerosis.…”

Circular RNA hsa_circ_0004543 Aggravates Cervical Cancer Development by Sponging MicroRNA hsa-miR-217 to Upregulate Hypoxia-Inducible Factor

“…Potential hsa_circ_0004543 sponged miRNAs were predicted with the online tool Circular RNA Interactome ( https://circinteractome.nia.nih.gov/ ) [ 28 ]. Potential mRNAs binding to hsa-miR-217 were predicted with the TargetScan online tool ( http://www.targetscan.org/ ) [ 29 ].…”

“…SYBR Green Premix Ex Taq™ II was mixed with cDNA and specific primers for qRT-PCR assay on a CFX96 TM real-time PCR detection system (Bio-Rad Laboratories, Hercules, USA). Relative gene expressions were calculated using the 2 −ΔΔ C t method with GAPDH as an internal control for mRNAs and circRNAs, and U6 as an internal control for miRNAs [ 27 , 29 ].…”

“…Cells cotransfected with hsa-miR-217 mimics or negative control (miR-NC), psiCHECK-2/hsa_circ_0004543 3′-UTR (WT), or psiCHECK-2/hsa_circ_0004543 3′-UTR mutated (MT) plasmid were used for hsa_circ_0004543 activity analysis, while cotransfected with psiCHECK-2/HIF-1Α 3′-UTR (WT) or psiCHECK-2/HIF-1Α 3′-UTR mutated (MT) plasmid were used for HIF-1Α activity analysis using Lipofectamine 3000. The dual-luciferase reporter assay kit was then used following the manufacturer's procedures [ 26 , 29 ].…”