Epigenetic silencing of MicroRNA-503 regulates FANCA expression in non-small cell lung cancer cell.
It is reported that MicroRNA-503 (miR-503) regulates cell apoptosis, and thus modulates the resistance of non-small cell lung cancer cells (NSCLC) to cisplatin. However, the exact role of miR-503 in NSCLC remains unknown. In the present study, the level of miR-503 expression in NSCLC was evaluated using realtime PCR, and the DNA methylation status within miR-503 promoter was analyzed by Combined Bisulfite Restriction Analysis (COBRA) or bisulfite-treated DNA sequencing assays (BSP). We found that the expression of miR-503 was significantly decreased in NSCLC tissues compared to normal tissues. A statistically significant inverse association was found between miR-503 methylation status and expression of the miR-503 in tumor tissues (P<0.001), and expression of miR-503 was restored by the demethylating agent 5-aza-2'-deoxycytidine, suggesting that methylation was associated with the transcriptional silencing. Then, we show that miR-503 targets a homologous DNA region in the 3'-UTR region of the Fanconi anemia complementation group A protein (FANCA) gene and represses its expression at the transcriptional level. Taken together, our results suggest that miR-503 regulates the resistance of non-small cell lung cancer cells to cisplatin at least in part by targeting FANCA.
Department of Respiratory Medicine, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000, China.
Ning
N
Li
Department of Internal Medicine-Oncology, The First Affiliated Hospital, Zhengzhou University, China.
Fangfang
F
Zhang
Department of Respiratory Medicine, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000, China. Electronic address: lisuyuntcm@163.com.
Suyun
S
Li
Department of Respiratory Medicine, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000, China.
Suzhen
S
Zhou
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use; D019175:DNA Methylation / Q000187:drug effects; D052217:Fanconi Anemia Complementation Group A Protein / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*
D000970:Antineoplastic Agents; D052217:Fanconi Anemia Complementation Group A Protein; C545473:MIRN503 microRNA, human; D035683:MicroRNAs; D002945:Cisplatin
FANCA; Methylation; Non-small cell lung cancer cell; miR-503