title: MicroRNA-134 modulates glioma cell U251 proliferation and invasion by targeting KRAS and suppressing the ERK pathway.
abstract: 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.
authors.affiliation: Department of Cell Biology, Harbin Medical University, Harbin, 150081, China.
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, No. 248 Xuefu Road, Nangang District, Harbin, 150086, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Pang
authors.affiliation: Land Reclamation of Community Health Service Stations, General Hospital of Heilongjiang Agricultural Reclamation Bureau, Harbin, 150090, China.
authors.forename: Cui
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Brain, The Affiliated Hospital of Tianjin Armed Police College, Tianjin, 300163, China.
authors.forename: Shijiang
authors.initials: S
authors.lastname: Zhong
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, No. 248 Xuefu Road, Nangang District, Harbin, 150086, China. shuangw_hmu@126.com.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005910:Glioma / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: C117307:KRAS protein, human; C569273:MIRN134 microRNA, human; D035683:MicroRNAs; D016283:Proto-Oncogene Proteins p21(ras)
keywords: ERK pathway; Glioma; Invasion; KRAS; MicroRNA-134; Proliferation