外泌体长链非编码 RNA UCA1 通过 microRNA-122-5p/ SOX2 轴调节宫颈癌干细胞自我更新和分化。

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

机构信息

Department of Gynecology, Xinxiang Central Hospital, NO. 56 Jinsui Road, Xinxiang, 453000, Henan, China.

Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450003, China.

出版信息

J Transl Med. 2021 May 30;19(1):229. doi: 10.1186/s12967-021-02872-9.

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 (CD133CaSki) 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 CD133CaSki 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 CD133CaSki cells. Silencing UCA1 or up-regulating miR-122-5p degraded SOX2 expression, and reduced invasion, migration and proliferation of CD133CaSki 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.

背景

越来越多的证据表明长链非编码 RNA（lncRNA）在宫颈癌（CC）中发挥作用。我们进行这项研究是为了探讨外泌体 lncRNA 尿路上皮癌相关 1（UCA1）通过海绵 microRNA-122-5p（miR-122-5p）和调节 SOX2 表达在 CC 干细胞中的作用。

方法

提取并鉴定 CC 干细胞（CD133CaSki）和外泌体。将合成的 UCA1 和 miR-122-5p 相关序列转染至 CaSki 细胞，提取 CaSki 细胞衍生的外泌体，然后与 CD133CaSki 细胞共培养。通过异位表达、敲低/耗竭和报告基因实验确定 UCA1 和 miR-122-5p 在 CC 干细胞自我更新和分化能力中的功能作用。进行体内实验验证体外结果。

结果

在 CaSki-Exo 中发现 UCA1 和 SOX2 上调，miR-122-5p 下调。外泌体促进 CD133CaSki 细胞的侵袭、迁移、增殖，抑制其凋亡。沉默 UCA1 或上调 miR-122-5p 降解 SOX2 表达，减少 CD133CaSki 细胞的侵袭、迁移和增殖，促进凋亡，并抑制裸鼠肿瘤体积和重量。