miR-107 regulates cisplatin chemosensitivity of A549 non small cell lung cancer cell line by targeting cyclin dependent kinase 8.
Previous studies demonstrated that the acquired drug resistance of non-small cell lung cancer (NSCLC) was related to deregulation of miRNAs. However, the effects of miR-107 and the mechanism through which miR-107 affects the cisplatin chemoresistance in NSCLC have not been reported. TaqMan RT-PCR or Western blot assay was performed to detect the expression of mature miR-107 and cyclin dependent kinase 8 (CDK8) protein. The viabilities of treated cells were analyzed using MTT assay. We found that the expression level of miR-107 in A549 cells was significantly lower than that in normal human bronchial epithelial cells (0.45 ± 0.26 vs. 1.00 ± 0.29, P = 0.032). The MTT assay showed that the A549 cells transfected with miR-107 mimics were significantly more sensitive to the therapy of cisplatin than control cells. A549 cells transfected with miR-107 mimics showed a decreased CDK8 protein expression. Downregulation of CDK8 expression by siRNAs, A549 cells became more sensitive to the therapy of cisplatin. In addition, the enhanced growth-inhibitory effect by the miR-107 mimic transfection was enhanced after the addition of CDK8 siRNA. In conclusion, the present study provides the first evidence that miR-107 plays a key role in cisplatin resistance by targeting the CDK8 protein in NSCLC cell lines, suggesting that miR-107 can be used to predict a patient's response to chemotherapy as well as serve as a novel potential maker for NSCLC therapy.
Department of Thoracic Surgery, Qingdao Municipal Hospital Qingdao 266011, Shandong Province, China.
Zhe
Z
Zhang
Department of Thoracic Surgery, Qingdao Municipal Hospital Qingdao 266011, Shandong Province, China.
Lu
L
Zhang
Department of Thoracic Surgery, Qingdao Municipal Hospital Qingdao 266011, Shandong Province, China.
Zhi-Yi
ZY
Yin
Department of Thoracic Surgery, Qingdao Municipal Hospital Qingdao 266011, Shandong Province, China.
Xing-Long
XL
Fan
Department of Thoracic Surgery, Qingdao Municipal Hospital Qingdao 266011, Shandong Province, China.
Bo
B
Hu
Department of Thoracic Surgery, Qingdao Municipal Hospital Qingdao 266011, Shandong Province, China.
Lun-Qing
LQ
Wang
Department of Thoracic Surgery, Qingdao Municipal Hospital Qingdao 266011, Shandong Province, China.
Di
D
Zhang
D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D056850:Cyclin-Dependent Kinase 8 / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D014162:Transfection
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C549045:MIRN107 microRNA, human; D035683:MicroRNAs; C095686:CDK8 protein, human; D056850:Cyclin-Dependent Kinase 8; D002945:Cisplatin
CDK8; Non small cell lung cancer; chemosensitivity; cisplatin; miR-107