Long non-coding RNA NEAT1 contributes to docetaxel resistance of prostate cancer through inducing RET expression by sponging miR-34a

Abstract

Background: Nuclear paraspeckle assembly transcript 1 (NEAT1) was demonstrated to serve as a carcinogenic long non-coding RNA (lncRNA) in multiple tumors including prostate cancer (PC). However, the potential biological role of NEAT1 in docetaxel resistance of PC and the underlying mechanism are largely unknown. Methods: Expressions of NEAT1 and miR-34a in PC tissues and cells were detected by qRT-PCR. The IC₅₀ value of docetaxel and apoptosis in PC cells were examined by CCK-8 assay and flow cytometry analysis, respectively. Bioinformatics software and a luciferase reporter assay were used to predict and confirm the potential targets of miR-34a. A tumor xenograft assay was employed to verify the effect of NEAT1 on docetaxel resistance of PC cells in vivo. Results: NEAT1 was upregulated and miR-34a was downregulated in PC tissues, parental PC cells and docetaxel-resistant PC cells. NEAT1 knockdown improved sensitivity to docetaxel in docetaxel-resistant PC cells. In addition, NEAT1 functioned as a ceRNA of miR-34a in docetaxel-resistant PC cells to positively regulate the expression of RET (rearranged during transfection). Moreover, miR-34a inhibition partially reversed NETA1-knockdown-induced sensitivity to docetaxel in docetaxel-resistant PC cells. NEAT1 overexpression partially overturned RET-knockdown-mediated sensitivity to docetaxel in docetaxel-resistant PC cells. Furthermore, NEAT knockdown enhanced docetaxel sensitivity of docetaxel-resistant PC cells in vivo. Conclusion: NEAT1 contributed to docetaxel resistance of PC through inducing RET expression by sponging miR-34a, implying that targeting the NEAT1/miR-34a/RET axis may be a potential application in improving chemotherapy of PC.