title: miR-130a can predict response to temozolomide in patients with glioblastoma multiforme, independently of O6-methylguanine-DNA methyltransferase.
abstract: BACKGROUND
  Currently, O6-methylguanine-DNA methyltransferase(MGMT) promoter methylation is the most convincing predictive biomarker for temozolomide (TMZ) response in patients with glioblastoma multiforme (GBM). However, technical obstacles prevent this biomarker from being applied widely. On the other hand, microRNAs (miRNAs) are easily investigated in the clinical setting using quantitative real-time polymerase chain reactions. This study aimed to identify miRNAs that could serve as predictive biomarkers for TMZ response.
  
  
  METHODS
  The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases were used to investigate the significance of associations between miRNA expression and overall survival (OS) in TMZ-treated patients with GBM. Cytotoxicity assays were used to validate the miRNAs' roles in the response of glioma cells to TMZ. Biological insights concerning the miRNAs were explored using gene set enrichment analysis (GSEA) and gene ontology (GO) analysis.
  
  
  RESULTS
  miR-130a was found to be significantly associated with OS in TMZ-treated patients from TCGA and the CGGA. In contrast, miR-130a appeared to be unassociated with OS in patients who only received radiotherapy. The TMZ cytotoxicity assay showed that miR-130a over-expression could sensitize response to TMZ in glioma cells. GSEA and GO analysis indicated that lower miR-130a could generate a more extensive response to oxidative stress, which in turn could elevate Ape1 and mediate resistance to TMZ. In vitro experiment verified that cells with lower miR-130a express higher Ape1 under oxidative stress.
  
  
  CONCLUSIONS
  Our data suggested that miR-130a could be a predictive marker for TMZ response in patients with GBM, independently of the mechanism by which MGMT acts as a biomarker. miR-130a could serve as a guide for treatment strategy selection in cases of GBM.
authors.affiliation: Cancer Center, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China. chenhuiyuan2013@126.com.
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Chen
authors.affiliation: University of South Florida, Tampa, FL, 33612, USA. li.xinyi.ib@gmail.com.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Li
authors.affiliation: Cancer Center, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China. liwenbin@ccmu.edu.cn.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Li
authors.affiliation: Hematology Oncology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics, Beijing Children's Hospital, Capital Medical University, Beijing, 100045, China. zhenghuyong@vip.sina.com.
authors.forename: Huyong
authors.initials: H
authors.lastname: Zheng
mesh_terms: D045744:Cell Line, Tumor; D015254:DNA Modification Methylases / Q000378:metabolism*; D045643:DNA Repair Enzymes / Q000378:metabolism*; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D016016:Proportional Hazards Models; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: C554019:MIRN130 microRNA, human; D035683:MicroRNAs; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide