Downregulation of long noncoding RNA HCP5 contributes to cisplatin resistance in human triple-negative breast cancer via regulation of PTEN expression

Abstract

BackgroundAbnormally expressed long non-coding RNA (lncRNA) is associated with the development of breast cancer and multidrug resistance. However, the molecular mechanism by which lncRNA regulates cisplatin (DDP) in triple-negative breast cancer (TNBC) remains unclear. MethodsDDP resistant cell line MDA-MB-231/DDP was established by gradually increasing doses of DDP. Abnormal expression of lncRNA between MDA-MB-231 and MDA-MB-231/DDP was evaluated with microarray. In addition, cell proliferation was evaluated by CCK-8 and Ki67 assays. Furthermore, cell apoptosis was evaluated by cell apoptosis and TUNEL assays. Western blotting assay was used to detect the protein expression. In vivo animal study was performed finally. ResultsHCP5 were significantly decreased in MDA-MB-231/DDP cells compared with MDA-MB-231 cells. Downregulation of HCP5 promoted DDP resistance in MDA-MB-231 cells by inhibiting PTEN expression. In contrast, overexpression of HCP5 reversed DDP resistance in MDA-MB-231/DDP cells by upregulating PTEN. In vivo experiments confirmed that overexpression of HCP5 inhibited DDP resistance in TNBC xenograft. ConclusionWe found that downregulation of HCP5 contributed to DDP resistance in TNBC, while overexpression of HCP5 reversed the resistance via upregulating PTEN level. Therefore, DDP combined with overexpression of HCP5 might be considered as a therapeutic approach for the treatment of DDP-resistant TNBC.