外泌体运载lncRNA-ROR在转移性去势抵抗性前列腺癌多西他赛耐药中的作用及机制研究

大部分转移性激素抵抗性前列腺癌（mCRPC）患者在接受多西他赛化疗后均会出现耐药，探寻多西他赛抵抗性mCRPC的耐药机制十分重要。研究发现长链非编码RNA（lncRNA）在前列腺癌的发生、发展中具有重要作用，但外泌体运载的lncRNA在mCRPC多西他赛耐药中的作用及机制尚不明确。我们前期研究发现，多西他赛耐药的mCRPC患者血清外泌体中lncRNA-ROR表达量显著增加，且lncRNA-ROR能够抑制mCRPC细胞对多西他赛的敏感性。为此，本研究拟从临床方面明确lncRNA-ROR与mCRPC患者的不良病理特征、多西他赛耐药和预后的关系；从基础角度探讨外泌体运载的lncRNA-ROR介导多西他赛耐药性产生及传递的作用，并进一步探索lncRNA-ROR通过竞争性抑制miR-145水平导致多西他赛耐药的分子机制。该课题的研究将为多西他赛抵抗性mCRPC的发生机制及治疗策略提供新的思路和靶点。

Although previous studies indicated that most of metastatic castrate-resistant prostate cancer (mCRPC) patients in the receiving docetaxel chemotherapy will appear resistance. Long-chain non-coding RNA (lncRNA) plays an important role in the development and progression of prostate cancer. However, the understanding of exosome-transmitted lncRNA in mediating the docetaxel resistance in mCRPC is largely unknown. In our preliminary study, we found upregulated lncRNA-ROR in serum correlated with poor docetaxel response in mCRPC patients. In addition, overexpressed lncRNA-ROR inhibited the sensitivity of docetaxel in mCRPC cells. On the basis of above findings, we first intend to investigate the relationship between lncRNA-ROR and the pathological features, docetaxel resistance and prognosis of mCRPC patients. Then, we plan to explore whether lncRNA-ROR could be incorporated into exosomes and transmitted to sensitive cells, and thus disseminating docetaxel resistance. In addition, we also want to clarify the mechanism of lncRNA-ROR mediating docetaxel resistance via competitively binding miR-145. The study will help provide a new insight into the pathogenesis and treatment strategies of docetaxel-resistant mCRPC.