Up-regulation of miR-370-3p restores glioblastoma multiforme sensitivity to temozolomide by influencing MGMT expression.
MicroRNAs (miRNA) are believed to play an important role in glioblastoma multiforme (GBM)chemotherapy. Our study aims to investigate potential miRNA biomarkers in GBM. Sixty GBM patients, which were given temozolomide (TMZ) chemotherapy and recurrent radiotherapy, were recruited. miRNA array was performed in cancerous and in paired normal tissues. Microarray results were further validated by a quantitative real-time PCR in selected tissues and GBM cell lines. TMZ resistance cells were developed and cell proliferation along with colony formation assays was determined. Our study employed H2AX formation and flow cytometry to analyse the role of miRNA in DNA damage and apoptosis. Our study illustrated 16 miRNA in which 9 were up-regulated and 7 down-regulated. and their differential expression were demonstrated in a recurrent GBM tissue. Among them, miRNA-370-3p demonstrated the highest level of down- regulation in tissues and in TMZ resistance cells. miRNA-370-3p mimic increased its expression and sensitivity of GBM cells to TMZ by suppressing the self-reparative ability of tumour cell DNA. O(6)-methylguanine-DNA methyltransferase (MGMT) was identified as the direct target gene of miR-370-3p, and it was found to be inversely correlated with miR-370-3p expression in tissue samples obtained. Thus, our study demonstrated a critical clinical role of an up-regulated miR-370-3p expression in glioblastoma multiforme chemotherapy sensitivity.
Department of Neurosurgery, Huaihe Hospital of Henan University, 475000, Kaifeng, Henan Province, 475000, China.
Yong-Tao
YT
Gao
Department of Neurosurgery, Huaihe Hospital of Henan University, 475000, Kaifeng, Henan Province, 475000, China.
Xiao-Bing
XB
Chen
Department of Neurosurgery, Huaihe Hospital of Henan University, 475000, Kaifeng, Henan Province, 475000, China.
Hong-Lin
HL
Liu
D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D049109:Cell Proliferation; D015254:DNA Modification Methylases / Q000235:genetics / Q000378:metabolism*; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D004273:DNA, Neoplasm; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
D018906:Antineoplastic Agents, Alkylating; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C526503:MIRN370 microRNA, human; D035683:MicroRNAs; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide