Abstract
Unfolded protein response (UPR) pathway is a promising target for cancer treatment because of its over-activation in different cancers and its role in tumorigenesis and chemotherapeutic drug resistance. Endoplasmic Reticulum Metallo Protease 1 (ERMP1) is overexpressed in cancers such as colorectal cancer. The ERMP1 role in UPR activation was previously reported in breast cancer. We aimed to investigate the ERMP1 role in the UPR activation in colorectal cancer. In this regard, ERMP1 gene was silenced in colorectal cancer HCT116 cell line using specific small hairpin RNA (shRNA). Then, UPR associated protein markers including inositol requiring enzyme 1 (IRE1α), activating transcription factor 6 (ATF-6), eukaryotic initiation factor 2α (eIF2α) and phosphorylated eIF2α (P- eIF2α) were evaluated using western blot. We found that ERMP1 gene expression and all of the above UPR associated protein markers were significantly decreased after ERMP1 gene silencing. Therefore, it seems that ERMP1 plays an important role in UPR activation. Since the overexpression of ERMP1 as a potential oncogene can highly activate the UPR pathway in colorectal cancer, it can be considered as a promising target for colorectal cancer treatment. However, further investigations are required to confirm these findings.
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Abbreviations
- ATF-6:
-
Activating transcription factor 6
- BiP:
-
Binding immunoglobulin protein
- CSC:
-
Cancer stem cell
- CRC:
-
Colorectal cancer
- ER:
-
Endoplasmic reticulum
- ERMP1:
-
Endoplasmic reticulum metallo protease 1
- eIF2α:
-
Eukaryotic initiation factor 2α
- Fxna:
-
Felix-ina
- GRP78:
-
Glucose-regulated protein 78
- HRP:
-
Horseradish peroxidase
- IRE1α:
-
Inositol requiring enzyme 1
- PBS:
-
Phosphate-buffered saline
- P- eIF2α:
-
Phosphorylated eIF2α
- PERK:
-
Protein kinase RNA-like ER kinase
- ROS:
-
Reactive oxygen species
- SDS-PAGE:
-
Sodium dodecyl sulfate-polyacrylamide
- shRNA:
-
Specific small hairpin RNA
- UPR:
-
Unfolded protein response
- XBP1:
-
X-box-binding protein-1
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Acknowledgments
The authors would like to express their sincere gratitude to Shiraz University of Medical Sciences for financially supporting the study (No. 16117). The authors would also like to acknowledge, Ms. Sarah Masoumi, English editor and internal manager of the Iranian Journal of Blood and Cancer for her valuable assistance in English editing of this manuscript.
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This work was financially supported by Shiraz University of Medical Sciences (Grant No.16117).
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M.Z and P.M coordinated and designed the study. M.Z acquired funding. S.D. and M.E. conducted the experiments. M. Z, P.M, S.Gh and S.V.H analyzed and interpreted the data. M.Z and S.D. wrote the manuscript, P.M. and S.Gh, and SV.H revised and approved the manuscript.
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Dastghaib, S., Mokarram, P., Erfani, M. et al. Endoplasmic reticulum Metallo protease 1, a triggering factor for unfolded protein response and promising target in colorectal cancer. Biologia 76, 2403–2411 (2021). https://doi.org/10.1007/s11756-021-00769-y
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DOI: https://doi.org/10.1007/s11756-021-00769-y