FAM60A promotes proliferation and invasion of colorectal cancer cells by regulating the Wnt/β-catenin signaling pathway.

Abstract

Background: Colorectal cancer (CRC) is one of the most detrimental tumors to human health. Although multimodal therapeutic approaches can improve patient survival rates, the prognosis for advanced-stage patients remains poor. It has been reported that family with sequence similarity 60, member A (FAM60A), a component of the SIN3 transcription regulator family member A (SIN3A)/histone deacetylase (HDAC) complex, plays a significant role in tumorigenesis. However, the precise function and mechanisms of action of FAM60A in CRC have not been fully elucidated. In this study, we aim to further delineate the role of FAM60A in CRC by assessing the protein expression levels of FAM60A and β-catenin in CRC tissues and to explore the potential mechanisms by which FAM60A may promote CRC cell proliferation and invasion through a suite of cellular assays.

Methods: Tumor tissues of 195 CRC patients and 65 adjacent non-neoplastic tissues were collected to construct tissue microarrays. The expression levels of FAM60A, c-Myc, cyclin D1, and β-catenin were detected using immunohistochemistry (IHC) staining, and the relationship between the results and the patients' clinicopathological characteristics and prognosis was analyzed. HCT116 and HT-29 cell lines with overexpression/knockdown of FAM60A were constructed. Western blot (WB) was used to detect the protein expression of FAM60A and β-catenin. Cell proliferation, apoptosis rate, cell cycle, and cell migration and invasion abilities were assessed using cell counting kit-8 (CCK-8) assay, flow cytometry, wound healing assay, and transwell assay, respectively.

Results: FAM60A demonstrated elevated expression in CRC tissues and was positively correlated with tumor infiltration depth, Ki67 proliferation index, and poor prognosis in patients. A positive correlation was observed between FAM60A and the expression of β-catenin, c-Myc, and cyclin D1, and patients with co-expression of FAM60A and β-catenin had a significantly higher rate of distant metastasis. The knockdown of FAM60A markedly reduced the proliferation, migration, and invasive capabilities of HCT116 cells, induced cell cycle arrest, and enhanced apoptosis, whereas its overexpression produced the converse effects. In HT-29 cells, FAM60A knockdown also reduced cell proliferation and impaired wound healing, with overexpression showing opposing outcomes. WB analysis revealed that modulation of FAM60A influenced β-catenin protein levels, suggesting a regulatory link between the two proteins.

Conclusions: FAM60A may be a key regulator factor that modulates proliferation and invasion in CRC cells via the Wnt/β-catenin signaling pathway. Elevated FAM60A expression is associated with an adverse prognosis in CRC, underscoring its potential as a prognostic biomarker.