<p>Tumor Suppressor microRNA-138 Suppresses Low-Grade Glioma Development and Metastasis via Regulating IGF2BP2</p>

Abstract

Background: Low-grade gliomas (LGG), approximately constitute one-third of all types of gliomas, are prone to relapse and metastasis. is reported to be dysregulated in diverse human tumors and mainly function as a tumor suppressor. In this study, we analyzed the expression profile and function of miR-138 in LGG. Methods: Quantitative PCR (qPCR) and public database bioinformatics analysis were performed to determine the miR-138 levels in LGG. MiR-138 overexpression in LGG cells was achieved by miR-138 mimics transfection. Cell proliferation was assessed by CCK8, EdU and colony formation assays. Cell invasion and migration were analyzed by transwell and woundhealing assays. Xenograft model was employed to study the role of miR-138 in LGG growth in vivo. The target of miR-138 was validated by multiple methods, such as luciferase reporter assay, RT-qPCR and Western blot. Bioinformatics analysis was conducted to explore the molecular mechanisms by which miR-138 contributed to LGG progression. Results: miR-138 was significantly downregulated in LGG tumor tissues and low expression of miR-138 was significantly associated with poor prognosis as well as relapse and metastasis in LGG patients. Functional analysis indicated that ectopic miR-138 expression suppressed LGG cell growth and invasive phenotype in vitro, and inhibited tumor development in vivo. Moreover, miR-138 directly targeted and repressed insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) by targeting the 3ʹ-UTR of IGF2BP2, inhibiting epithelial to mesenchymal transition (EMT) to attenuate LGG aggressiveness. In addition, we found that elevated IGF2BP2 expression correlates with poor survival of LGG patients. Conclusion: miR-138 may function as a tumor inhibitor by directly inhibiting IGF2BP2 and suppressing EMT in the progression of LGG.

Screening and functional prediction of differentially expressed circular RNAs in human glioma of different grades

“…A recent study also confirmed this conclusion. It has been reported that miR-138 may function as a tumor inhibitor by directly inhibiting IGF2BP2 and suppressing EMT during the progression of LGG [ 56 ]. Hence, RBPs of circRNAs in this paper merit further study.…”

The role of IGF2BP2, an m6A reader gene, in human metabolic diseases and cancers

“…M6A-RNA methylation refers to methylation of adenosine bases at position N6 in 3′UTRs near the stop codons but within the internal long exons [ 10 , 11 ]. Modified IGF2BP2 participates in the development and progression of multiple metabolic disease and cancers, including diabetes [ 2 ], obesity [ 12 ], fatty liver [ 13 ], breast cancer [ 14 ], colorectal carcinoma [ 15 ], esophageal adenocarcinoma [ 16 ], glioma [ 17 ], hepatocellular carcinoma [ 18 ], lung cancer [ 19 ], pancreatic cancer [ 20 ] and many others.…”

MicroRNA‑138 modulates glioma cell growth, apoptosis and invasion through the suppression of the AKT/mTOR signalling pathway by targeting CREB1

“…Recent studies have indicated that miR-138 may act as a tumour suppressor in various cancers, such as ATC, NSCLC and OSCC ( 7 , 9 , 10 ). Notably, certain studies demonstrated that miR-138 inhibits GBM cell proliferation by suppressing the EZH2-CDK4/6-pRb-E2F1 signalling loop and suppresses low-grade glioma development and metastasis by regulating IGF2BP2 ( 19 , 26 ). However, Chan et al demonstrated that miR-138 acts as an oncogene in glioma stem cells (GSCs) ( 27 ).…”

“…Notably, certain miRNAs, such as miR-92a-3p, miR-221, miR-222 and miR-21, exert opposite effects on glioma cells and GSCs ( 29 , 30 ). This obvious paradox may be attributed to the fact that miRNAs may target several important downstream signal molecules, some of which may have opposite functions, which may partially explain why miR-138 could act as either an onco-miR in GSCs ( 27 ) or a tumour suppressor in glioma cells ( 19 , 26 ). The present study confirmed that miR-138 exerts an antitumour effect in glioma cells through the dephosphorylation of AKT/mTOR by targeting CREB1, which should be further investigated in future studies.…”