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CircCOL1A2 Sponges MiR-1286 to Promote Cell Invasion and Migration of Gastric Cancer by Elevating Expression of USP10 to Downregulate RFC2 Ubiquitination Level

  • Li, Hang (Gastroenterology and Hepatobiliary Surgery, The Affiliated Hospital of Hangzhou Normal University) ;
  • Chai, Lixin (Gastroenterology and Hepatobiliary Surgery, The Affiliated Hospital of Hangzhou Normal University) ;
  • Ding, Zujun (Gastroenterology and Hepatobiliary Surgery, The Affiliated Hospital of Hangzhou Normal University) ;
  • He, Huabo (Gastroenterology and Hepatobiliary Surgery, The Affiliated Hospital of Hangzhou Normal University)
  • Received : 2021.12.27
  • Accepted : 2022.05.07
  • Published : 2022.07.28

Abstract

Gastric cancers (GC) are generally malignant tumors, occurring with high incidence and threatening public health around the world. Circular RNAs (circRNAs) play crucial roles in modulating various cancers, including GC. However, the functions of circRNAs and their regulatory mechanism in colorectal cancer (CRC) remain largely unknown. This study focuses on both the role of circCOL1A2 in CRC progression as well as its downstream molecular mechanism. Quantitative polymerase chain reaction (qPCR) and western blot were adopted for gene expression analysis. Functional experiments were performed to study the biological functions. Fluorescence in situ hybridization (FISH) and subcellular fraction assays were employed to detect the subcellular distribution. Luciferase reporter, RNA-binding protein immunoprecipitation (RIP), co-immunoprecipitation (Co-IP), RNA pull-down, and immunofluorescence (IF) and immunoprecipitation (IP) assays were used to explore the underlying mechanisms. Our results found circCOL1A2 to be not only upregulated in GC cells, but that it also propels the migration and invasion of GC cells. CircCOL1A2 functions as a competing endogenous RNA (ceRNA) by sequestering microRNA-1286 (miR-1286) to modulate ubiquitin-specific peptidase 10 (USP10), which in turn spurs the migration and invasion of GC cells by regulating RFC2. In sum, CircCOL1A2 sponges miR-1286 to promote cell invasion and migration of GC by elevating the expression of USP10 to downregulate the level of RFC2 ubiquitination. Our study offers a potential novel target for the early diagnosis and treatment of GC.

Keywords

Acknowledgement

This work was supported by "Study on the role and mechanism of long non-coding RNA ENRPD1-AS1 mediating the up-regulation of METTL3 expression in promoting gastric cancer" (2021KY250).

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