Background: Colorectal cancer (CRC) is one of the leading causes of cancer-related death, and up to 50% of individuals will suffer relapse. Although transmembrane and immunoglobulin domain-containing protein 1 (TMIGD1) was found to be a protective factor in several renal and intestinal diseases, the specific role of TMIGD1 in CRC remains unclear. Objective: To determine the tumor suppressor TMIGD1 expression and its function in inhibiting CRC. Methods: We analyzed three Gene Expression Omnibus (GEO) datasets through the GEO2R online tool to obtain the set of differentially expressed genes (DEGs) between CRC and normal tissues, and further analyzed the TMIGD1 gene's expression in databases. Real-time quantitative polymerase chain reaction and western blot assays were used to investigate expression of TMIGD1. Transwell and wound healing assays were performed to detect the migration and invasion ability. Cell Counting Kit-8 (CCK-8) and colony formation assays were used to evaluate cell proliferation. In vivo studies were conducted to illustrate the tumorigenicity. Results: We found that the TMIGD1 gene is one of the highly downregulated genes in CRC through bioinformatic analysis. We also showed that downregulation of TMIGD1 is associated with poor overall survival rate of CRC based on The Cancer Genome Atlas (TCGA) databases. In addition, we showed that overexpression of TMIGD1 protein significantly impaired the metastasis and proliferation ability of the CRC cells. Finally, TMIGD1 also repressed subcutaneous tumorigenesis of CRC cells in vivo. Conclusion: Our findings indicate that downregulation of TMIGD1 may promote CRC progression and invasion. Therefore, TMIGD1 may serve as a biomarker for CRC prognoses.
Keywords: TMIGD1; colorectal cancer; prognostic marker; tumor suppressor.