Constructed the ceRNA network and predicted a FEZF1-AS1/miR-92b-3p/ZIC5 axis in colon cancer

Mol Cell Biochem. 2023 May;478(5):1083-1097. doi: 10.1007/s11010-022-04578-y. Epub 2022 Oct 11.

Abstract

The purpose of this study was to identify the role of FEZF1-AS1 in colon cancer and predicted the underlying mechanism. We extracted sequencing data of colon cancer patients from The Cancer Genome Atlas database, identified the differential expression of long noncoding RNA, microRNA, and messenger RNA, constructed a competitive endogenous RNA network, and then analyzed prognosis. Then, we used the enrichment analysis databases for functional analysis. Finally, we studied the FEZF1-AS1/miR-92b-3p/ZIC5 axis. We detected the expression of FEZF1-AS1, miR-92b-3p, and ZIC5 via quantitative reverse transcription-PCR, transfected colon cancer cell RKO with lentivirus and conducted FEZF1-AS1 knockdown, and performed cancer-related functional assays. It indicated that many RNA in the competitive endogenous RNA network, such as ZIC5, were predicted to be related to overall survival of colon cancer patients, and enrichment analysis showed cancer-related signaling pathways, such as PI3K/AKT signaling pathway. The expression of FEZF1-AS1 and ZIC5 was significantly higher and that of miR-92b-3p was lower in the colon cancer than in the normal colon tissues. FEZF1-AS1 promoted the migration, proliferation, as well as invasion of RKO. According to the prediction, FEZF1-AS1 and ZIC5 might competitively bind to miR-92b-3p, leading to the weakening of the inhibitory impact of miR-92b-3p on ZIC5 and increasing expression of ZIC5, thus further activating the PI3K/AKT signaling pathway, which led to the occurrence and development of colon cancer. The study suggested that FEZF1-AS1 might be an effective diagnosis biomarker for colon cancer.

Keywords: Biomarker; Colon cancer; Competing endogenous RNA network; FEZF1-AS1; Survival; lncRNA.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Colonic Neoplasms* / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Long Noncoding* / genetics
  • Signal Transduction
  • Transcription Factors / metabolism

Substances

  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • MicroRNAs
  • RNA, Long Noncoding
  • ZIC5 protein, human
  • DNA-Binding Proteins
  • Transcription Factors