Long non-coding RNA CDKN2B antisense RNA 1 gene contributes to paclitaxel resistance in endometrial carcinoma

Abstract

Endometrial cancer (EC) is the most common malignancy of the female reproductive tract. In this study, we clarified the clinical significance of CDKN2B antisense RNA 1 (CDKN2B-AS) gene, and its effects on paclitaxel sensitivity in EC. Firstly, CDKN2B-AS gene was highly expressed in EC tissues and cell lines. The high-expression of CDKN2B-AS gene was associated with high pathological grade and low paclitaxel sensitivity of EC tissues. Knockdown of CDKN2B-AS gene sensitized Ishikawa/PA and HEC1A/PA cells to paclitaxel, and promoted paclitaxel-induced cytotoxicity. Secondly, the low-expression of miR-125a-5p was closely associated with low paclitaxel sensitivity of EC cells, and up-regulation of miR-125a-5p could increase paclitaxel sensitivity of Ishikawa/PA and HEC1A/PA cells. MiR-125a-5p also mediated the suppressive effects of knockdown of CDKN2B-AS on paclitaxel resistance in EC cells. Thirdly, B-cell lymphoma-2 (Bcl2) and Multidrug Resistance-Associated Protein 4 (MRP4) genes were target genes of miR-125a-5p, which modulated paclitaxel resistance of Ishikawa/PA and HEC1A/PA cells through targeted silencing Bcl2 and MRP4. In conclusion, high-expression of CDKN2B-AS is associated with a poor response to paclitaxel of EC patients, and knockdown of CDKN2B-AS inhibits paclitaxel resistance through miR-125a-5p-Bcl2/MRP4 pathway in EC patients. Our findings help elucidate the molecular mechanisms of chemoresistance in EC patients.