The role of HM13 expression and its relationship to PI3K/Akt and p53 signaling pathways in colorectal cancer

Abstract

Histocompatibility minor 13 (HM13) is a signal sequence stubbed intramembrane cleavage catalytic protein. Increasing evidence supports the association among HM13 expression, tumor-infiltrating immune cells (TIICs), and cancer. However, its role on formation and progression of colorectal cancer (CRC) has not been explored. In this study, we aim to identify the role and function of HM13 on the progression of CRC and explore the possible mechanism. The findings of our study indicate that HM13 is significantly upregulated in colorectal cancer (CRC) compared to normal colorectal tissues (P< 0.001). Moreover, the elevated expression of HM13 is associated with unfavorable prognosis in CRC patients. Furthermore, our results demonstrate that the overexpression of HM13 contributes to enhanced proliferation and migration, as well as suppressed apoptosis, in SM480 and HCT116 cell lines (P<0.001). Conversely, the downregulation of HM13 (shHM13) yields opposite effects. Additionally, the administration of LY294003 and nutlin-3 effectively inhibits proliferation and migration, while promoting apoptosis in HCT116 cells (P<0.001). However, the presence of HM13 counteracts these changes. In an in vivo study, the knockdown of HM13 (shHM13) significantly reduces tumor growth and the proportion of Ki-67 positive cells, while increasing the percentage of tunel-positive cells (P<0.001). Also, shHM13 decreased the level of p-PI3K/PI3K and p-AKT/AKT, upregulated p53 and p21 activities. It can thus be concluded that HM13 might be a novel oncogene in CRC and regulates proliferation, migration and apoptosis by modulating the PI3K/Akt and p53 signaling pathways.