title: miR-124 Acts as a Tumor Suppressor in Glioblastoma via the Inhibition of Signal Transducer and Activator of Transcription 3.
abstract: MicroRNAs are important regulators of multiple cellular processes, and aberrant miRNA expression has been observed in human glioblastoma (GBM). The present study was to evaluate the level of miR-124 and signal transducer and activator of transcription 3 (STAT3) in GBM tissues and cells. We further investigated the molecular mechanisms of miR-124 and STAT3 in GBM cell lines U87 and U251. Here, we found that miR-124 expression was downregulated in GBM tissues and U87 and U251 cells (all p < 0.001) but not associated with blood routine (RBC, WBC count, etc.) and liver and renal function indicators (all p > 0.05). By contrast, STAT3 was upregulated. Furthermore, the expression of miR-124 was inversely proportional to that of STAT3 mRNA or protein (p = 0.013, p = 0.015, respectively). In vitro studies demonstrated that the overexpression of miR-124 played a suppressor role in the proliferation of U87 and U251 cells and promoted cell apoptosis. Luciferase reporter assays confirmed that miR-124 binding to the 3'-UTR regions of STAT3 inhibited the expression of STAT3 in U87 and U251 cells. However, the inhibitor of miR-124 promoted the expression of STAT3 and cell proliferation. In conclusion, our data suggest that miR-124 may have a potential role in treatment of GBM patients and that miR-124 is a novel regulator of invasiveness and tumorigenicity in GBM cells by targeting STAT3. The miR-124/STAT3 pathway may be a useful therapeutic agent in GBM patients.
authors.affiliation: Department of Laboratory Medicine, Second Hospital of Hebei Medical University, No. 215 Hepingxi Road, Shijiazhuang, Hebei, 050000, China. lwhaohebei@163.com.
authors.forename: Weihao
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Laboratory Medicine, Children's Hospital of Hebei Province, Shijiazhuang, Hebei, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Laboratory Medicine, Second Hospital of Hebei Medical University, No. 215 Hepingxi Road, Shijiazhuang, Hebei, 050000, China.
authors.forename: Junhua
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Laboratory Medicine, Second Hospital of Hebei Medical University, No. 215 Hepingxi Road, Shijiazhuang, Hebei, 050000, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ji
authors.affiliation: Department of Laboratory Medicine, Second Hospital of Hebei Medical University, No. 215 Hepingxi Road, Shijiazhuang, Hebei, 050000, China.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Medicine, Second Hospital of Hebei Medical University, No. 215 Hepingxi Road, Shijiazhuang, Hebei, 050000, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Blood Transfusion, Hebei Provincial Chest Hospital, Shijiazhuang, Hebei, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011485:Protein Binding / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; C509207:MIRN124 microRNA, human; D035683:MicroRNAs; D050796:STAT3 Transcription Factor; D025521:Tumor Suppressor Proteins
keywords: GBM; STAT3; miR-124