LncRNA DLEU2 contributes to Taxol resistance of gastric cancer cells through regulating the miR-30c-5p-LDHA axis

Abstract

Gastric cancer (GC) is a human malignancy which is associated with high mortality rate and poor prognosis. In addition to surgery, chemo- and radio-therapies are effective strategies against GC at advanced or metastatic stage. Taxol is a traditionally anti-cancer drug which is applied to various types of cancer. However, development of drug resistance limited the anti-cancer effects of Taxol. Currently, the biological roles and mechanisms of non-coding RNA DLEU2 in Taxol resistant GC remain unclear. This study reported that DLEU2 was significantly upregulated and miR-30c-5p was remarkedly downregulated in gastric tumours and cell lines. Silencing DLEU2 or overexpression of miR-30c-5p effectively increased the Taxol sensitivity of GC cells. Through bioinformatics analysis, RNA pull-down and luciferase assay, we demonstrated that DLEU2 sponged miR-30c-5p to block its expression in GC cells. Moreover, from the established Taxol resistant GC cell line, we detected remarkedly upregulated DLEU2 and downregulated miR-30c-5p expressions and significantly elevated glucose metabolism. Under low glucose condition, Taxol resistant cells were more susceptible to Taxol. In addition, we showed overexpression of miR-30c-5p blocked glucose metabolism through inhibiting the LDHA, a glucose metabolism key enzyme by direct targeting the 3′UTR of LDHA. Finally, rescue experiments validated that restoration of miR-30c-5p in DLEU2-overexpressing Taxol resistant GC cells effectively overcame the DLEU2-promoted Taxol resistance. In summary, this study uncovered new roles and molecular mechanisms of the lncRNA DLEU2-promoted Taxol resistance of gastric cancer cells, presenting the DLEU2-miR-30c-5p-LDHA-glucose metabolism axis a potentially therapeutic target for treatment of Taxol resistant GC.