MicroRNA-134 modulates glioma cell U251 proliferation and invasion by targeting KRAS and suppressing the ERK pathway
Dysregulated microRNA-134 (miR-134) has been observed in glioma carcinogenesis, and studies suggested that the ERK pathway plays vital roles in glioma cell growth and proliferation. However, the fundamental relationship between miR-134 and the ERK pathway in glioma has not been fully explained. As a result, this study was aimed to explore the underlying functions of miR-134 in human glioma. Intentionally overexpressed or inhibited miR-134 expression resulted from the transfection of miR-134 mimics, or miR-134 inhibitor within glioma cell line U251 was detected using RT-PCR. Both cell counting kit-8 (CCK-8) assays and Transwell assays were carried out to clarify the proliferation and invasion of U251 cells transfected with miR-134 mimics or miR-134 inhibitors. Our findings showed that miR-134 was significantly downexpressed in glioma tissues, and low miR-134 expression was significantly related to high histopathological grades. However, upregulated miR-134 expression restrained the proliferation and invasion of U251 cells in vitro. Kirsten rat sarcoma viral oncogene (KRAS), a vital factor for the ERK pathway, was directly targeted by miR-134 through its binding with the 3′-UTR of KRAS in glioma. Furthermore, KRAS expression exhibited a positive correlation with the activity of the ERK pathway. Overexpression of KRAS without 3′-UTR partly offsets the suppressive effect of miR-134 on glioma progression. Our data also indicated that miR-134 negatively modulated glioma progression and upregulated miR-134 triggered aberrant activation of the ERK pathway by targeting KRAS. Therefore, miR-134 might be considered as a benign therapeutic target of glioma.
KeywordsMicroRNA-134 Glioma Proliferation Invasion KRAS ERK pathway
This study was supported by Scientific Research Item of Health Department in Heilongjiang Province (No. 2011–076) and Youth Science Funds of Heilongjiang Province (No. QC2011C130).
Compliance of ethical standards
The ethics committee of the Second Affiliated Hospital of Harbin Medical University thoroughly reviewed the protocol of this study, and eventually, study approval was obtained. All participants signed the consent prior to the commencement of molecular experiments.
Conflicts of interest
- 7.Michaud DS, Gallo V, Schlehofer B, Tjonneland A, Olsen A, Overvad K, et al. Reproductive factors and exogenous hormone use in relation to risk of glioma and meningioma in a large European cohort study. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2010;19:2562–9.CrossRefGoogle Scholar
- 13.Hassan T, Smith SG, Gaughan K, Oglesby IK, O’Neill S, McElvaney NG, et al. Isolation and identification of cell-specific microRNAs targeting a messenger RNA using a biotinylated anti-sense oligonucleotide capture affinity technique. Nucleic Acids Res. 2013;41:e71.CrossRefPubMedCentralPubMedGoogle Scholar
- 27.Szerlip NJ, Pedraza A, Chakravarty D, Azim M, McGuire J, Fang Y, et al. Intratumoral heterogeneity of receptor tyrosine kinases EGFR and PDGFRA amplification in glioblastoma defines subpopulations with distinct growth factor response. Proc Natl Acad Sci U S A. 2012;109:3041–6.CrossRefPubMedCentralPubMedGoogle Scholar
- 44.Shin YM, Yun J, Lee OJ, Han HS, Lim SN, An JY, et al. Diagnostic value of circulating extracellular mir-134, mir-185, and mir-22 levels in lung adenocarcinoma-associated malignant pleural effusion. Cancer research and treatment : official journal of Korean Cancer Association. 2014;46:178–85.CrossRefGoogle Scholar
- 53.Kitamura K, Seike M, Okano T, Matsuda K, Miyanaga A, Mizutani H, et al. Mir-134/487b/655 cluster regulates TGF-beta-induced epithelial-mesenchymal transition and drug resistance to gefitinib by targeting MAGI2 in lung adenocarcinoma cells. Mol Cancer Ther. 2014;13:444–53.CrossRefPubMedGoogle Scholar