环状 RNA circNFATC3 通过海绵吸附 miR-9-5p 而上调 SDC2 的表达，促进宫颈癌的发展。

Circular RNA circNFATC3 acts as a miR-9-5p sponge to promote cervical cancer development by upregulating SDC2.

机构信息

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang City, 110004, China.

出版信息

Cell Oncol (Dordr). 2021 Feb;44(1):93-107. doi: 10.1007/s13402-020-00555-z. Epub 2020 Sep 9.

DOI:10.1007/s13402-020-00555-z

PMID:32902825

Abstract

PURPOSE

Circular RNAs (circRNAs) constitute a class of regulatory RNAs that are thought to play important roles in tumor initiation and progression. Several studies have reported that circRNAs may be involved in various biological processes via networks of competing endogenous RNAs (ceRNAs). However, the regulatory roles and underlying mechanisms of circRNAs in cervical cancer (CC) still largely remain to be resolved.

METHODS

CircNFATC3 (hsa_circ_0005615) expression was assessed in CC cell lines (SiHa, H8) using circRNA microarray analysis, whereas qRT-PCR was used to detect circNFATC3 and miR-9-5p expression in primary human CC tissues and cell lines. The tumor promoting role of circNFATC3 was verified in CC cells using a series of functional assays, and interactions between circNFATC3, miR-9-5p and syndecan-2 (SDC2) were investigated using dual-luciferase reporter assays. SDC2 protein expression was detected using Western blotting and immunohistochemistry. The tumor promoting role of circNFATC3 was confirmed in vivo using a CC xenograft model.

RESULTS

We found that circNFATC3 expression was upregulated in primary CC tissues and positively correlated with CC tumor size and stromal invasion. In addition, we found that exogenous circNFATC3 overexpression enhanced the proliferation, migration and invasion of HeLa cells, while its knockdown reduced the malignancy of SiHa cells. We also found that circNFATC3 may act directly as a miR-9-5p sponge to regulate SDC2 expression and its downstream signaling pathways, thereby enhancing CC development.

CONCLUSION

Our data indicate that circNFATC3 sponges miR-9-5p to regulate SDC2 expression and, thereby, to promote CC tumor development.

摘要

目的

环状 RNA（circRNAs）构成了一类调节 RNA，被认为在肿瘤的发生和发展中发挥重要作用。有几项研究报道，circRNAs 可能通过竞争内源性 RNA（ceRNA）网络参与各种生物学过程。然而，circRNAs 在宫颈癌（CC）中的调节作用和潜在机制在很大程度上仍有待解决。

方法

使用 circRNA 微阵列分析评估 CC 细胞系（SiHa、H8）中的 circNFATC3（hsa_circ_0005615）表达，而 qRT-PCR 用于检测原发性人 CC 组织和细胞系中的 circNFATC3 和 miR-9-5p 表达。使用一系列功能测定验证 circNFATC3 在 CC 细胞中的促肿瘤作用，并使用双荧光素酶报告测定研究 circNFATC3、miR-9-5p 和 syndecan-2（SDC2）之间的相互作用。使用 Western blot 和免疫组化检测 SDC2 蛋白表达。使用 CC 异种移植模型体内验证 circNFATC3 的促肿瘤作用。

结果

我们发现 circNFATC3 在原发性 CC 组织中表达上调，并与 CC 肿瘤大小和基质浸润呈正相关。此外，我们发现外源性 circNFATC3 过表达增强了 HeLa 细胞的增殖、迁移和侵袭，而其敲低则降低了 SiHa 细胞的恶性程度。我们还发现 circNFATC3 可能直接作为 miR-9-5p 的海绵来调节 SDC2 表达及其下游信号通路，从而促进 CC 的发展。