The Role of Endoplasmic Reticulum Metallo Protease 1 on Autophagy Pathway in HCT-116 Colorectal Cancer Cell Line

Autophagy and the unfolded protein response (UPR) are mechanisms with dual roles in both maintaining cellular homeostasis and controlling the progression of various diseases such as cancer. Therefore, the identification of different molecules and proteins involved in the regulation of these pathways may contribute to finding new therapeutic targets. A member of the M28 family of the metallopeptidases, endoplasmic reticulum metalloprotease 1 (ERMP1), is overexpressed in cancers such as colorectal cancer. The role of this protein in UPR activation was previously reported in breast cancer. We aimed to evaluate the role of ERMP1 in the activation of autophagy and apoptosis in colorectal cancer. Methods: ERMP1 gene silencing was performed using specific small hairpin RNA (shRNA) in the HCT-116 colorectal cancer cell line. Then, autophagy-associated protein markers including Beclin 1, p62, and LC3II were evaluated via western blotting. The effect of ERMP1 knockdown on cellular apoptosis was also assessed by propidium iodide staining flow cytometry analysis. Statistical analysis was performed using SPSS software version 20. Results: All three autophagy markers increased significantly in the ERMP1-silenced HCT116 cell lines compared with negative control cells (P<0.05). It seems that ERMP1 silencing inhibits autophagy at the flux stage. However, ERMP1 knockdown had no significant effect on HCT-116 apoptotic cell death (P>0.05). Conclusion: The oncogenic protein, ERMP1, activates autophagy in the HCT-116 colorectal cancer cell line. Targeting ERMP1 may be considered as a proper approach in colorectal cancer therapy. Further investigations are required to confirm these results.