Exosomal lncRNA UCA1 modulates cervical cancer stem cell self-renewal and differentiation through microRNA-122-5p/SOX2 axis

被引:50
作者
Gao, Zhihui [1 ]
Wang, Qianqing [1 ]
Ji, Mei [2 ]
Guo, Xiangcui [1 ]
Li, Li [1 ]
Su, Xiaoke [1 ]
机构
[1] Xinxiang Cent Hosp, Dept Gynecol, 56 Jinsui Rd, Xinxiang 453000, Henan, Peoples R China
[2] Zhengzhou Univ, Dept Gynecol, Affiliated Hosp 1, Zhengzhou 450003, Peoples R China
关键词
Cervical cancer stem cells; Exosomes; LncRNA UCA1; MicroRNA-122-5p; SOX2; Proliferation; GASTRIC-CANCER; PROLIFERATION; MIR-122-5P; EXPRESSION; APOPTOSIS; MIGRATION; INVASION;
D O I
10.1186/s12967-021-02872-9
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
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页数:11
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