Downregulation of Ascl2 promotes cell apoptosis by enhancing autophagy in colorectal cancer cells

Background: Colorectal cancer (CRC) is the third most common cancer, according to recently published literature. While the incidence and the mortality of CRC has decreased due to effective cancer screening measures, there has been an increase in the number of young patients diagnosed with colon cancer due to unclear reasons. As a target molecule of the Wnt signaling pathway, Ascl2 is an important marker of CRC stem cells and plays an important role in maintaining the nature of colon cancer stem/precursor cells. However, the role of Ascl2 in autophagy in CRC cells is rarely elucidated. Methods: In this study, we found that Ascl2 was increased in CRC compared with adjacent tissue. Downregulation of Ascl2 in CRC cells could suppress proliferation and invasion, and induce apoptosis, of CRC cells. Moreover, we found that autophagy-relative protein LC3 increased after Ascl2 knockdown. Furthermore, we treated CRC cells with autophagy inhibitors 3- MA (3-Methyladenine) and CQ (Chloroquine). Results: The results showed that autophagy inhibitors could prevent apoptosis, which was induced by Ascl2 knockdown. Finally, we confirmed that the downregulation of Ascl2 in CRC cells could alleviate the pathological process in vivo by xenograft experiment. Conclusions: Our findings indicated that si-Ascl2 (small/short interfering) exerted a tumor suppression function in CRC by inducing autophagic cell death, and suggest that Ascl2 targeted therapy represents a novel strategy for CRC treatment.

Automated summary

The study revealed that increased expression of Ascl2 in colorectal cancer is associated with tumor proliferation and invasion, while its downregulation can induce apoptosis. Additionally, Ascl2 knockdown led to increased autophagy in cancer cells, which could be prevented by autophagy inhibitors. Overall, targeting Ascl2 for therapy could represent a novel strategy for treating colorectal cancer by inducing autophagic cell death.