Abstract: Objective To investigate the effects of family with sequence similarity 50 member A (FAM50A) on the proliferation, migration, and apoptosis of colorectal cancer (CRC) cells and explore its molecular regulatory mechanisms. Methods The expression characteristics and clinical relevance of FAM50A in pan⁃cancer and CRC were analyzed through using TCGA and GTEx databases. The expression of FAM50A protein in 5 pairs of  CRC tissues and adjacent normal tissues were performed by Western blot, as well as in five CRC cell lines (LOVO, RKO, HCT116, SK⁃CO⁃1, SNU175). Stable FAM50A⁃knockdown HCT116 and RKO cell lines were established. The effects on cellular proliferation, migration, and tumorigenesis ability in vivo were assessed through CCK⁃8 assays, Transwell assays, wound healing experiments, and a nude mouse xenograft model. Apoptosis rates and cell cycle were detected via flow cytometry, while the changes in apoptosis⁃related protein expression detected by Western blot. Results Bioinformatics analysis indicated that FAM50A was highly expressed in 16 cancer types, including lung adenocarcinoma and colon adenocarcinoma (all P<0.05). FAM50A mRNA expression levels were significantly higher in CRC tissues than in normal tissues (P<0.001), with high expression correlated with poorer prognosis. FAM50A expression was markedly increased in colorectal adenocarcinoma patients compared with mucinous adenocarcinoma patients (P<0.001). Clinical sample analysis also showed that FAM50A protein expression levels were significantly higher in CRC tissues than in adjacent normal tissues (P<0.001). Functional experiments revealed that FAM50A knockdown suppressed proliferation, migration, and xenograft tumor growth in HCT116 and RKO cells (all P<0.01) and significantly induced apoptosis (all P<0.001). The Western blot results showed that FAM50A knockdown significantly up⁃regulated the expression levels of c⁃Caspase 3, c⁃Caspase 8, c⁃Caspase 9, and c⁃PARP (all P<0.05). Conclusions FAM50A is overexpressed in CRC and associated with poor prognosis. Targeted FAM50A knockdown inhibits CRC cell proliferation and migration by activating the Caspase 3/PARP apoptotic pathway, suggesting its  potential as a therapeutic target for CRC.

Key words: Colorectal cancer, FAM50A, Proliferation, Migration, Apoptosis