Exosomal lncRNA UCA1 modulates cervical cancer stem cell self-renewal and differentiation through microRNA-122-5p/SOX2 axis
Zhihui Gao, Qianqing Wang, Mei Ji, Xiangcui Guo, Li Li, Xiaoke Su
Abstract
Abstract Background There is growing evidence discussing the role of long non-coding RNAs (lncRNAs) in cervical cancer (CC). We performed this study to explore the impact of exosomal lncRNA urothelial cancer-associated 1 (UCA1) in CC stem cells by sponging microRNA-122-5p (miR-122-5p) and regulating SOX2 expression. Methods CC stem cells (CD133 + CaSki) and exosomes were extracted and identified. The synthesized UCA1- and miR-122-5p-related sequences were transfected into CaSki cells, CaSki cells-derived exosomes were extracted and then co-cultured with CD133 + CaSki cells. The functional roles of UCA1 and miR-122-5p in self-renewal and differentiation ability of CC stem cells were determined using ectopic expression, knockdown/depletion and reporter assay experiments. An in vivo experiment was performed to verify the in vitro results. Results Up-regulated UCA1 and SOX2 and down-regulated miR-122-5p were found in CaSki-Exo. Exosomes promoted invasion, migration, proliferation and restrained apoptosis of CD133 + CaSki cells. Silencing UCA1 or up-regulating miR-122-5p degraded SOX2 expression, and reduced invasion, migration and proliferation of CD133 + CaSki cells while advanced apoptosis and suppressed the tumor volume and weight in nude mice. Conclusion Our study provides evidence that CaSki-Exo can promote the self-renewal and differentiation ability of CC stem cells while silencing UCA1 or up-regulating miR-122-5p restrains self-renewal and differentiation of CC stem cells.