circCOL12A1 induce epithelial–mesenchymal transition and facilitates oncogenesis in gastric cancer via miR-30b-3p/ZEB1 axis

作者：Xiaochong Zhang, Li Wang, Xiaoling Zhao, Xiao‐Peng Tian, Qiuxiang Lei, Yuandong Li, Limin Hui, Liangfang Tian, Shurui Xie, Dengxiang Liu · 发表于：Research Square · 年份：2022 · DOI：10.21203/rs.3.rs-1560888/v1 · 研究领域：Circular RNAs in diseases、MicroRNA in disease regulation、RNA Research and Splicing

Abstract Circular RNAs (circRNAs) play an essential regulatory role in gene expression. Abnormally expressed circRNAs contribute to the occurrence and development of multiple cancers including gastric cancer (GC). However, studies regarding circRNAs in GC remain inadequate. In this study, we used high-throughput screening assays and discovered that circCOL12A1 was significantly increased in GC tissues compared with that in normal gastric tissues. Overexpression of circCOL12A1 enhanced cell proliferation, whereas depletion of circCOL12A1 reduced GC cell migration and epithelial–mesenchymal transition (EMT) by regulating EMT-related gene expression. Mechanistically, circCOL12A1 sponged miR-30b-3p and inhibited miR-30b-3p activity and increased the expression of the EMT-related transcriptional factor, ZEB1. miR-30b-3p expression was lower in GC tissue and correlated with poor survival of GC patients. By contrast, ZEB1 was highly expressed in GC and played a role in promoting GC cell migration and EMT. Furthermore, we confirmed that upregulation of ZEB1 via circCOL12A1-induced inhibition of miR-30b-3p resulted in GC cell proliferation and migration by regulating the EMT process. We demonstrated a pivotal role of circCOL12A1 in regulating proliferation and migration in cancer cells, and the results suggest a therapeutic benefit from targeting the circCOL12A1/miR-30b-3p/ZEB1 pathway in GC.