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

Journal of Translational Medicine

Mei Ji¹  Zhihui Gao²  Xiangcui Guo²  Xiaoke Su²  Li Li²  Qianqing Wang² 

[1] Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, 450003, Zhengzhou, China;Department of Gynecology, Xinxiang Central Hospital, NO. 56 Jinsui Road, 453000, Xinxiang, Henan, China;

关键词: Cervical cancer stem cells;    Exosomes;    LncRNA UCA1;    MicroRNA-122-5p;    SOX2;    Proliferation;   

DOI  :  10.1186/s12967-021-02872-9

来源: Springer

【 摘 要 】

BackgroundThere 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.MethodsCC 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.ResultsUp-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.ConclusionOur 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.

【 授权许可】

CC BY