Drug resistance limits the efficacy of chemotherapy in human cancers. Previous studies reported that long noncoding RNA colon cancer-associated transcript 1 (CCAT1) regulated progression of prostate cancer (PCa). However, the potential role of CCAT1 in the sensitivity of paclitaxel (PTX) in PCa and its mechanism remain largely unknown. The PTX-resistant PCa cells were established in PC3 and DU145 cells by increasing concentrations of PTX. The expressions of CCAT1, microRNA-24-3p (miR-24-3p) and fascin1 (FSCN1) were measured by quantitative real-time polymerase chain reaction. The viability and apoptosis were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, flow cytometry and western blot, respectively. The interaction among CCAT1, miR-24-3p and FSCN1 was explored by luciferase activity, RNA immunoprecipitation, RNA pull-down and western blot, respectively. Results showed that the expressions of CCAT1 were up-regulated and miR-24-3p was down-regulated in PCa and PTX-resistant PCa cells (PC3-TXR and DU145-TXR). Knockdown of CCAT1 or overexpression of miR-24-3p inhibited survival rate, half maximal inhibitory concentration (IC50) of PTX but increased apoptosis in PC3-TXR and DU145-TXR cells after treatment of PTX. miR-24-3p was bound to CCAT1 and its abrogation reversed knockdown of CCAT1-mediated increase of PTX sensitivity in PC3-TXR and DU145-TXR cells. Moreover, FSCN1 restoration attenuated miR-24-3p-mediated inhibition of PTX resistance. Besides, FSCN1 level was enhanced in PCa and PTX-resistant PCa cells and regulated by CCAT1 and miR-24-3p. Our data suggested interference of CCAT1 contributed to PTX sensitivity in PCa by regulating miR-24-3p and FSCN1, indicating a novel avenue for treatment of PCa through regulating chemoresistance.

中文翻译：

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抑制lncRNA CCAT1可以通过调节miR-24-3p和FSCN1增强紫杉醇在前列腺癌中的敏感性。

耐药性限制了化学疗法在人类癌症中的功效。先前的研究报道，长的非编码RNA结肠癌相关转录本1（CCAT1）调节前列腺癌（PCa）的进程。但是，CCAT1在紫杉醇（PTX）在PCa中的敏感性及其机制中的潜在作用仍然未知。通过增加PTX的浓度，在PC3和DU145细胞中建立了抗PTX的PCa细胞。通过定量实时聚合酶链反应测量CCAT1，microRNA-24-3p（miR-24-3p）和fascin1（FSCN1）的表达。分别通过3-（4,5-二甲基-2-噻唑基）-2,5-二苯基-2-H-溴化四氮唑测定，流式细胞术和western blot检测存活率和凋亡。通过荧光素酶活性，RNA免疫沉淀，CCAT1，miR-24-3p和FSCN1之间的相互作用 RNA下拉和蛋白质印迹。结果显示，在PCa和PTX耐药PCa细胞（PC3-TXR和DU145-TXR）中，CCAT1的表达上调，而miR-24-3p的表达下调。抑制CCAT1或miR-24-3p的过表达抑制了PTX的存活率，最大抑制浓度（IC50）的一半，但增加了PC3-TXR和DU145-TXR细胞的凋亡。miR-24-3p与CCAT1结合，其废除可逆转PC3-TXR和DU145-TXR细胞中CCAT1介导的PTX敏感性增加的敲低。此外，FSCN1恢复减弱了miR-24-3p介导的PTX抗性抑制。此外，FSCN1水平在PCa和耐PTX的PCa细胞中升高，并受CCAT1和miR-24-3p调控。