miR-20a enhances cisplatin resistance of human gastric cancer cell line by targeting NFKBIB.
Drug resistance of cancer cells can be regulated by the dysregulated miRNAs, and sustained NFκB activation also plays an important role in tumor resistance to chemotherapy. Here, we sought to investigate whether there was a correlation between miR-20a and the NFκB pathway to clarify the effects that miR-20a exerted on gastric cancer (GC) chemoresistance. We found that miR-20a was significantly upregulated in GC plasma and tissue samples. In addition, it was upregulated in GC plasma and tissues from patients with cisplatin-resistant gastric cancer cell line SGC7901/cisplatin (DDP). And the upregulation of miR-20a was concurrent with the downregulation of NFKBIB (also known as IκBβ) as well as upregulation of p65, livin, and survivin. The luciferase activity suggested that NFKBIB was the direct target gene of miR-20a. Transfection of miR-20a inhibitor could increase NFKBIB level; downregulate the expression of p65, livin, and survivin; and lead to a higher proportion of apoptotic cells in SGC7901/DDP cells. Conversely, ectopic expression of miR-20a dramatically decreased the expression of NFKBIB; increased the expression of p65, livin, and survivin; and resulted in a decrease in the apoptosis induced by DDP in SGC7901 cells. Taken together, our findings suggested that miR-20a could promote activation of the NFκB pathway and downstream targets livin and survivin by targeting NFKBIB, which potentially contributed to GC chemoresistance.
Department of Oncology, The First People's Hospital of Kunshan Affiliated with Jiangsu University, Suzhou, 215300, People's Republic of China.
Yiping
Y
Du
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People's Republic of China.
Mingxia
M
Zhu
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People's Republic of China.
Xin
X
Zhou
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People's Republic of China.
Zebo
Z
Huang
Department of Radiation Oncology, Jiangsu Cancer Hospital, No. 42 Bai Zi Ting, Nanjing, 210009, People's Republic of China.
Jun
J
Zhu
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People's Republic of China.
Jing
J
Xu
Department of General Surgery, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People's Republic of China.
Gongming
G
Cheng
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People's Republic of China.
Yongqian
Y
Shu
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People's Republic of China.
Ping
P
Liu
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People's Republic of China. zhuwei@njmu.edu.cn.
Wei
W
Zhu
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People's Republic of China. kingtsh@163.com.
Tongshan
T
Wang
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry*; D017209:Apoptosis; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation; D002945:Cisplatin / Q000737:chemistry*; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism*; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000473:pathology*; D000077022:Survivin; D051996:Transcription Factor RelA / Q000378:metabolism; D015854:Up-Regulation
D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; C419866:BIRC7 protein, human; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D051034:Inhibitor of Apoptosis Proteins; C534451:MIRN20a microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; C498143:RELA protein, human; D000077022:Survivin; D051996:Transcription Factor RelA; D002945:Cisplatin
Cisplatin resistance; NFKBIB; NFκB; miR-20a