miR-20a enhances cisplatin resistance of human gastric cancer cell line by targeting NFKBIB
- 334 Downloads
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.
KeywordsmiR-20a NFκB NFKBIB Cisplatin resistance
The authors are grateful to the fund support by the National Natural Science Foundation of China (grant number 81201705 and 81201796) and the Natural Science Foundation of Jiangsu Province (grant number BK2012442).
Conflicts of interest
- 6.Michaelis M, Rothweiler F, Barth S, Cinatl J, van Rikxoort M, Loschmann N, et al. Adaptation of cancer cells from different entities to the MDM2 inhibitor nutlin-3 results in the emergence of p53-mutated multi-drug-resistant cancer cells. Cell Death Dis. 2011;2:e243.CrossRefPubMedPubMedCentralGoogle Scholar