Circular RNA circNFATC3 acts as a miR-9-5p sponge to promote cervical cancer development by upregulating SDC2.
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.
['Ma|Ningye|N|', 'Li|Xinhui|X|', 'Wei|Heng|H|', 'Zhang|Huijie|H|', 'Zhang|Shulan|S|http://orcid.org/0000-0003-3639-5211']
D000818:Animals D001483:Base Sequence D063646:Carcinogenesis D045744:Cell Line, Tumor D002465:Cell Movement D049109:Cell Proliferation D018450:Disease Progression D005260:Female D015972:Gene Expression Regulation, Neoplastic D006801:Humans D008819:Mice, Nude D035683:MicroRNAs D008875:Middle Aged D008954:Models, Biological D009361:Neoplasm Invasiveness D000079962:RNA, Circular D053669:Syndecan-2 D015854:Up-Regulation D002583:Uterine Cervical Neoplasms
circNFATC3 miR-9-5p Sponging Cervical cancer SDC2 EMT