Li Zewu, Niu Huanfu, Qin Qianqian, Yang Sanhui, Wang Qin, Yu Chunna, Wei Zefeng, Jin Zhenzhen, Wang Xuenan, Yang Aijun, Chen Xiaoli
Center for Reproductive Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, China.
Center for Clinical Skills Training, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, China.
Mol Ther Nucleic Acids. 2019 Sep 6;17:92-101. doi: 10.1016/j.omtn.2019.05.007. Epub 2019 May 24.
The aim of this study was to explore the roles of the long noncoding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) on cisplatin resistance in ovarian cancer and the underlying mechanisms. We investigated the expression of lncRNAs in 3 paired cisplatin-sensitive and cisplatin-resistant tissues of ovarian cancer by microarray analysis. The qRT-PCR analysis was to investigate the expression pattern of UCA1 in cisplatin-resistant ovarian cancer patient tissues and cell lines. Then we examined the effects of UCA1 on cisplatin resistance in vitro and in vivo. In this study, UCA1 was observed to be upregulated in cisplatin-resistant patient tissues and cell lines. Knockdown of UCA1 inhibited cell proliferation and promoted the cisplatin-induced cell apoptosis in ovarian cancer cells. Then we demonstrated that repressed UCA1 promoted the miR-143 expression and miR-143 could bind to the predicted binding site of UCA1. Furthermore, we found that miR-143 displayed its role via modulating the FOSL2 expression. Importantly, we demonstrated that UCA1 was upregulated in serum exosomes from cisplatin-resistant patients. In summary, our study demonstrated that UCA1 modulates cisplatin resistance through the miR-143/FOSL2 pathway in ovarian cancer.
本研究旨在探讨长链非编码RNA(lncRNA)尿路上皮癌相关1(UCA1)在卵巢癌顺铂耐药中的作用及潜在机制。我们通过微阵列分析研究了3对卵巢癌顺铂敏感和耐药组织中lncRNAs的表达。qRT-PCR分析旨在研究UCA1在顺铂耐药卵巢癌患者组织和细胞系中的表达模式。然后我们在体外和体内检测了UCA1对顺铂耐药的影响。在本研究中,观察到UCA1在顺铂耐药患者组织和细胞系中上调。敲低UCA1可抑制卵巢癌细胞增殖并促进顺铂诱导的细胞凋亡。然后我们证明,抑制UCA1可促进miR-143表达,且miR-143可与UCA1的预测结合位点结合。此外,我们发现miR-143通过调节FOSL2表达发挥作用。重要的是,我们证明顺铂耐药患者血清外泌体中UCA1上调。总之,我们的研究表明,UCA1通过miR-143/FOSL2途径调节卵巢癌的顺铂耐药。