Circular RNA circNFATC3 acts as a miR-9-5p sponge to promote cervical cancer development by upregulating SDC2
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ORIGINAL PAPER
Circular RNA circNFATC3 acts as a miR-9-5p sponge to promote cervical cancer development by upregulating SDC2 Ningye Ma 1 & Xinhui Li 1 & Heng Wei 1 & Huijie Zhang 1 & Shulan Zhang 1 Accepted: 21 August 2020 # International Society for Cellular Oncology 2020
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. Keywords Cervical cancer . circNFATC3 . miR-9-5p . SDC2 . Sponging . EMT
1 Introduction Cervical cancer (CC) is the fourth most common female malignancy worldwide and, as such, represents a major global health challenge [1]. Since high-risk human papillomavirus Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13402-020-00555-z) contains supplementary material, which is available to authorized users. * Shulan Zhang [email protected] Ningye Ma [email protected] 1
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang City 110004, China
(HPV) subtypes cause almost all CCs, HPV screening and vaccination programs are considered to be effective disease prevention tools [2]. In China, CC is the second most common female malignancy and the average age of patients with CC has decreased in the last 20 years, being dropped by 5 years in the last decade. The majority of patients with CC is diagnosed at an advanced stage or with locally advanced c
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