Oncogenic circular RNA Hsa‐circ‐000684 interacts with microRNA‐186 to upregulate ZEB1 in gastric cancer

• Published in: The FASEB journal 2020-06, Vol.34 (6), p.8187-8203
• Main Authors: Lin, Sen, Song, Suzhen, Sun, Rong, Zhang, Mingbao, Du, Yating, Zhang, Dongdong, Xu, Weihua, Wang, Hongbo
• Format: Article
• Language: English
• Subjects: Adult; Aged; angiogenesis; Animals; Carcinogenesis - genetics; Cell Line; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; circular RNA hsa‐circ‐000684; Disease Progression; Down-Regulation - genetics; Female; gastric cancer; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs - genetics; microRNA‐186; Middle Aged; Oncogenes - genetics; RNA, Circular - genetics; RNA, Messenger - genetics; Stomach Neoplasms - genetics; Up-Regulation - genetics; ZEB1; Zinc Finger E-box-Binding Homeobox 1 - genetics
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.201903246R

Circular RNAs (circRNAs) function as modulators of microRNAs (miRNAs) and are often involved in cancer progression. This study aims to investigate the underlying mechanism by which circRNA hsa‐circ‐000684 promotes the progression of gastric cancer (GC). Expression of hsa‐circ‐000684 and that of ZEB1 mRNA were elevated while microRNA‐186 (miR‐186) expression was downregulated in GC cell lines and clinical tissues. In addition, the effects of hsa‐circ‐000684 on the proliferation, migration, invasion, and tube formation of GC cells were examined through gain‐and loss‐of‐function experiments. Furthermore, we introduced tumor xenografts into nude mice to better understand these effects in vivo. Either knockdown of hsa‐circ‐000684 or upregulation of miR‐186 inhibited GC cell proliferation, migration, invasion, and tube formation in vitro, and reduced the xenograft tumor growth in nude mice. Moreover, we found that hsa‐circ‐000684 and ZEB1 directly bound to miR‐186. Hsa‐circ‐000684 increased the expression of ZEB1 by binding to miR‐186. The tumor suppressive effects of hsa‐circ‐000684 knockdown were reversed by inhibition of miR‐186. Collectively, our data show that hsa‐circ‐000684 reduces the miR‐186 expression which leads to an increase in the ZEB1 expression and, consequently, promotion of GC progression.