A novel protein encoded by circINSIG1 reprograms cholesterol metabolism by promoting the ubiquitin-dependent degradation of INSIG1 in colorectal cancer.

ABSTRACT: Hypoxia is a hallmark of solid tumors and leads to the metabolic reprogramming of cancer cells. The role of epigenetic regulation between hypoxia and aberrant cholesterol metabolism in colorectal cancer (CRC) remains elusive. Hypoxia-responsive circular RNAs (circRNAs) were identified by high throughput RNA sequencing between CRC cells cultured under normoxia or hypoxia. The protein-coding potential of circINSIG1 was identified by polysome profiling and LC-MS. The function of circINSIG1 was validated in vitro and in vivo by gain or loss of function assays. Mechanistic results were concluded by immunoprecipitation analyses. A novel hypoxia-responsive circRNA named circINSIG1 was identified, which was upregulated in CRC tissues and correlated with advanced clinical stages and poor survival.

SUBMITTER: Xiong L 

PROVIDER: S-EPMC10122405 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature