Ningye Ma1, Xinhui Li1, Heng Wei1, Huijie Zhang1, Shulan Zhang2. 1. Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang City, 110004, China. 2. Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang City, 110004, China. zsl0909@sina.com.
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.
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.
Authors: A Aishanjiang; N Rouzi; Z Jiao; L Wang; K Wusainahong; N Wumanjiang; M Musha; M Niyazi Journal: Eur Rev Med Pharmacol Sci Date: 2018-04 Impact factor: 3.507
Authors: Stephanie Tuminello; Yian Zhang; Lei Yang; Nedim Durmus; Matija Snuderl; Adriana Heguy; Anne Zeleniuch-Jacquotte; Yu Chen; Yongzhao Shao; Joan Reibman; Alan A Arslan Journal: Int J Environ Res Public Health Date: 2022-04-22 Impact factor: 4.614