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.

Keywords:

• Taxol resistance
• lncRNA DLEU2
• miR-30c-5p
• glucose metabolism
• Warburg effect
• LDHA

Disclosure statement

This study corresponding with Helsinki declaration was approved by the Ethics Committee of Shenzhen Luohu People’s Hospital.

Conflict of research interests

The author(s) declared no potential conflicts of interest.

Consent for publication

All patients provided written informed consent for publication.

Author contributions

H.J.L. designed the experiments. W.G.X. B.Zh. and H.J.L. carried out the experiments and analyzed the data. All authors participated into the manuscript preparation. All authors reviewed the manuscript.

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.