The dysregulation of microRNAs (miRNAs) has been demonstrated to contribute to drug resistance of cancer cells, and sustained nuclear factor (NF)κB activation is also pivotal in tumor resistance to chemotherapy. In the present study, an essential role for miRNA (miR)-20a was identified in the regulation of gastric cancer (GC) chemoresistance. The expression level of miR‑20a was assayed by reverse transcription‑quantitative polymerase chain reaction. Additionally, 3-(4,5-dimethylthiazol-2‑yl)-2,5-diphenyltetrazolium bromide was used to detect the drug‑resistance phenotype changes of cancer cells associated with upregulation or downregulation of miR‑20a. Protein expression levelss were measured by western blotting and immunohistochemistry. Flow cytometry was used to detect cisplatin‑induced apoptosis. It was found that miR‑20a was markedly upregulated in GC plasma and tissue samples. Additionally, miR‑20a was upregulated in GC plasma and tissues from patients with cisplatin (DDP) resistance, and in the DPP‑resistant gastric cancer cell line (SGC7901/DDP). The expression of miR‑20a was inversely correlated with the expression of cylindromatosis (CYLD). Subsequently, the assessment of luciferase activity verified that CYLD was a direct target gene of miR‑20a. Treatment with miR‑20a inhibitor increased the protein expression of CYLD, downregulated the expression levels of p65, livin and survivin, and led to a higher proportion of apoptotic cells in the SGC7901/DDP cells. By contrast, ectopic expression of miR‑20a significantly repressed the expression of CYLD, upregulated the expression levels of p65, livin and survivin, and resulted in a decrease in the apoptosis induced by DDP in the SGC7901 cells. Taken together, the results of the present study suggested that miR‑20a directly repressed the expression of CYLD, leading to activation of the NFκB pathway and the downstream targets, livin and survivin, which potentially induced GC chemoresistance. Altering miR‑20a expression may be a potential therapeutic strategy for the treatment of chemoresistance in GC in the future.

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.

Circulating miR-21 may be a suitable diagnostic biomarker for CRC with moderate sensitivity and specificity. Further studies should evaluate the diagnostic value of miR-21 for CRC in the future.