RAI14 Regulated by circNFATC3/miR-23b-3p axis Facilitates Cell Growth and Invasion in Gastric Cancer
Xinxin Yan, MingZhi Zhang, Bingbing Li, Xia Ji, Hongjin Wu, Qingyu Zhang
Abstract
Circular RNAs (circRNAs) have been proved to act crucial roles in multiple malignancies including gastric cancer (GC). Retinoic acid induced 14 (RAI14) acts as an oncogene in human cancers, but the underlying mechanisms by which RAI14 is regulated by circRNA/miRNA axis remain elusive. The clinical value of RAI14, miR-23b-3p and circNFATC3 was estimated by The Cancer Genome Atlas and fluorescence in situ hybridization. The interplay between miR-23b-3p and RAI14 or circNFATC3 was determined by qRT-PCR, Western blot, luciferase gene report and RIP assays. Biological function assays and a subcutaneous xenograft model were executed to unveil the role of circNFATC3/miR-23b-3p/RAI14 axis in GC cells. As a consequence, upregulation of RAI14 and circNFATC3 or downregulation of miR-23b-3p was associated with poor prognosis in patients with GC. Restored miR-23b-3p depressed cell proliferation, colony formation, and cell invasion by targeting RAI14, whereas RAI14 facilitated cell progression and reversed the anti-tumor effects of miR-23b-3p in GC cells. Then, circNFATC3 had a co-localization with miR-23b-3p in the cytoplasm in GC tissue cells and could act as a sponge of miR-23b-3p in GC cell line. Silencing of circNFATC3 inhibited cell growth and in vivo tumorigenesis by upregulating miR-23b-3p and downregulating RAI14. In conclusion, our findings indicated that RAI14 facilitated cell growth and invasion and was regulated by circNFATC3/miR-23b-3p axis in GC.