A novel DNA binding protein encoded by circZNF131 inhibits the growth of gastric cancer by suppressing CTBP2 transcription.

Circular RNAs (circRNAs) play critical roles in the occurrence of gastric cancer (GC). However, the roles of proteins encoded by circRNAs in GC remain largely unknown. This study aimed to investigate the role of ZNF131-354aa in GC. circZNF131 overexpression plasmids and short hairpin RNAs were used to overexpress and silence circZNF131 expression levels, respectively. Mass spectrometry, co-immunoprecipitation, and Western blotting were used to identify the circZNF131-encoded protein, named ZNF131-354aa. Chromatin immunoprecipitation assay was used to examine the DNA-binding activity of ZNF131-354aa. A subcutaneous tumor model was established in nude mice to examine the effects of ZNF131-354aa on GC growth. Overexpression of circZNF131 was found to inhibit the proliferation, migration and invasion of GC cells, while knockdown of circZNF131 had the opposite effect. Furthermore, immunoprecipitation and mass spectrometry verified that circZNF131 encoded a 40.5 kDa protein, ZNF131-354aa. ZNF131-354aa was shown to inhibit GC progression. ZNF131-354aa was found to be degraded by tripartite motif-containing 28 (TRIM28)-mediated ubiquitination. Moreover, ZNF131-354aa was found to promote E-cadherin and phosphatase and tensin homolog (PTEN) expression by interacting with the intron of the C-terminal binding protein 2 (CTBP2) gene and repressing its expression. In conclusion, ZNF131-354aa acts as a tumor suppressor in GC by inhibiting CTBP2 transcription.