Panoply™ Human RGMA Over-expressing Stable Cell Line

Breast cancer (BC) is the most common cancer among women worldwide, and investigating aberrantly expressed genes helps elucidate the mechanisms of tumorigenesis and identify novel therapeutic strategies. Although RGMA has recently been identified as a tumor suppressor gene, its specific biological functions and regulatory mechanisms in breast cancer remain unclear. Here, researchers found that RGMA expression is downregulated in breast cancer tissues-particularly in metastatic samples-compared to non-tumor breast tissues, and that low RGMA expression correlates with a poor prognosis. Further investigation revealed that DNMT1 and DNMT3A are recruited to the RGMA promoter region, inducing aberrant hypermethylation and thereby suppressing RGMA expression in breast cancer. Conversely, RGMA overexpression inhibits breast cancer cell proliferation and colony formation while promoting apoptosis; in contrast, RGMA knockdown accelerates proliferation and suppresses apoptosis in both in vitro and in vivo experiments. Reversing RGMA promoter methylation using 5-Aza-CdR restores RGMA expression and inhibits tumor growth. In summary, DNMT1- and DNMT3A-mediated hypermethylation of the RGMA promoter leads to the downregulation of RGMA, and low RGMA expression promotes breast cancer growth by activating the FAK/Src/PI3K/AKT signaling pathway.

To investigate the functional significance of RGMA expression, researchers established an RGMA-overexpressing cell line (Figure 1A). Previous studies have demonstrated that RGMA inhibits the migration and invasion of bladder cancer (BC) cells; in the present study, EdU assay results showed that RGMA overexpression significantly suppressed DNA synthesis activity. Furthermore, CCK-8 and colony formation assays revealed that the proliferation and colony-forming capabilities of RGMA-overexpressing cells were inhibited (Figure 1B-F). Flow cytometry analysis also indicated that RGMA overexpression promoted apoptosis in BC cells (Figure 1G and H). These findings suggest that RGMA overexpression inhibits the malignant proliferation of BC cells and promotes their apoptosis.

Figure 1. RGMA overexpression inhibited BC cells proliferation and induced cell apoptosis. (Li Y, et al., 2022)