Low expression of ARHGAP40 in colorectal cancer facilitates tumor progression by activating the RhoA pathway

Background ARHGAP40, downregulated in various tumors including basal cell carcinoma, has an unclear role in colorectal cancer (CRC). This study aimed to elucidate the function and clinical significance of ARHGAP40 in CRC. Methods Immunohistochemistry (IHC) was utilized to assess the quantity of ARHGAP40 protein in both tumor and normal tissues. RNA interference (RNAi) and lentiviral vectors were used to either overexpress ARHGAP40 or knockdown ARHGAP40 in CRC cells. The CCK-8 test was used to measure cell proliferation, and flow cytometry was used to measure cell apoptosis. Scratch and Transwell tests were used to explore how ARHGAP40 affected the migration and invasion of CRC cells. RNA-sequence, western blotting, RhoA pull-down, and coimmunoprecipitation (co-IP) methods were used to figure out how ARHGAP40 affects CRC cells. Results Researchers discovered that the expression of ARHGAP40 was significantly lower in human colorectal cancer tissues. This low level of ARHGAP40 expression was linked to tumor differentiation, invasion depth, lymph node metastasis, TNM stage, and a poor outcome in CRC patients. Overexpression of ARHGAP40 also greatly decreased cell proliferation, made it harder for cells to migrate and invade, and raised the apoptosis rates of CRC cells. Also, RhoA activity was enhanced after ARHGAP40 was knocked down. Conclusion ARHGAP40 levels downregulated in CRC, and it might be possible for it to act as a new tumor suppressor in CRC by controlling RhoA activity.