C8orf48 inhibits the tumorigenesis of colorectal cancer by regulating the MAPK signaling pathway

Abstract

AimsColorectal cancer (CRC) is a leading cause of cancer-related death globally. Thus, in this study, we aimed to investigate chromosome 8 open reading frame 48 (C8orf48) as a biomarker for early detection of CRC. Main methodsRNA expression and methylation profiles were downloaded from The Cancer Genome Atlas (TCGA) database. Cell proliferation, migration and invasion assays were performed to confirm the function of C8orf48 in CRC cells. Dual-luciferase reporter assay was used to identify that C8orf48 was the direct target of miR-556. Genomics of Drug Sensitivity in Cancer (GDSC) database, gene set enrichment analysis (GSEA) and western blot analysis were performed to explore the mechanism of C8orf48. Key findingswe found that C8orf48 is down-regulated in clinical samples of CRC tissues. Enrichment analysis showed that C8orf48 is associated with methylation biomarkers in CRC, and TCGA database confirmed that the methylation of C8orf48 is up-regulated in the early stage of CRC. We further revealed that the overexpression of C8orf48 decreased CRC cell proliferation, migration and invasion. Luciferase reporter indicated that C8orf48 was the direct target of the oncogene miR-556. Additionally, we used GDSC database, GSEA database and western blot analysis to demonstrate that C8orf48 plays a suppressor role in CRC by inhibiting MAPK signaling pathway. SignificanceC8orf48 was identified as a biomarker for early detection of CRC for the first time, and might provide novel information for CRC prediction and therapy.