The Role of endoplasmic reticulum metallo protease 1 on Autophagy Pathway in HCT-116 Colorectal Cancer Cell Line

Background: Autophagy and unfolded protein response (UPR) are mechanisms with dual roles in both maintaining the cellular homeostasis and progression of various diseases such as cancer. Therefore, identification of different molecules and proteins involved in the regulation of these pathways may con...

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Autores principales: Mozhdeh Zamani, Sanaz Dastghaib, Mehran Erfani, Seyed Vahid Hosseini, Pooneh Mokarram
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Publicado: Shiraz University of Medical Sciences 2021
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spelling oai:doaj.org-article:bd64c61cae1f425e9236a4357b5b8a242021-11-14T06:50:42ZThe Role of endoplasmic reticulum metallo protease 1 on Autophagy Pathway in HCT-116 Colorectal Cancer Cell Line2783-243010.30476/acrr.2021.91373.1102https://doaj.org/article/bd64c61cae1f425e9236a4357b5b8a242021-06-01T00:00:00Zhttps://colorectalresearch.sums.ac.ir/article_47640_aea27b9ced7d5fabbf87fd7c0ec75c52.pdfhttps://doaj.org/toc/2783-2430Background: Autophagy and unfolded protein response (UPR) are mechanisms with dual roles in both maintaining the cellular homeostasis and progression of various diseases such as cancer. Therefore, identification of different molecules and proteins involved in the regulation of these pathways may contribute to find new therapeutic targets. A member of the M28 family of the metallopeptidases, Endoplasmic Reticulum Metallo Protease 1 (ERMP1), is overexpressed in cancers such as colorectal cancer. The role of this protein in the 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 HCT-116 colorectal cancer cell line. Then, autophagy associated protein markers including Beclin 1, p62 and LC3II were evaluated using western blot. 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 were 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 colorectal cancer cell line. Targeting of ERMP1 may be considered as a proper approach in colorectal cancer therapy. Further investigations are required to confirm these results.Mozhdeh ZamaniSanaz DastghaibMehran ErfaniSeyed Vahid HosseiniPooneh MokarramShiraz University of Medical Sciencesarticleermp1colorectal neoplasmtarget therapyendoplasmic reticulum stressMedicineRENIranian Journal of Colorectal Research, Vol 9, Iss 2, Pp 63-68 (2021)
institution DOAJ
collection DOAJ
language EN
topic ermp1
colorectal neoplasm
target therapy
endoplasmic reticulum stress
Medicine
R
spellingShingle ermp1
colorectal neoplasm
target therapy
endoplasmic reticulum stress
Medicine
R
Mozhdeh Zamani
Sanaz Dastghaib
Mehran Erfani
Seyed Vahid Hosseini
Pooneh Mokarram
The Role of endoplasmic reticulum metallo protease 1 on Autophagy Pathway in HCT-116 Colorectal Cancer Cell Line
description Background: Autophagy and unfolded protein response (UPR) are mechanisms with dual roles in both maintaining the cellular homeostasis and progression of various diseases such as cancer. Therefore, identification of different molecules and proteins involved in the regulation of these pathways may contribute to find new therapeutic targets. A member of the M28 family of the metallopeptidases, Endoplasmic Reticulum Metallo Protease 1 (ERMP1), is overexpressed in cancers such as colorectal cancer. The role of this protein in the 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 HCT-116 colorectal cancer cell line. Then, autophagy associated protein markers including Beclin 1, p62 and LC3II were evaluated using western blot. 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 were 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 colorectal cancer cell line. Targeting of ERMP1 may be considered as a proper approach in colorectal cancer therapy. Further investigations are required to confirm these results.
format article
author Mozhdeh Zamani
Sanaz Dastghaib
Mehran Erfani
Seyed Vahid Hosseini
Pooneh Mokarram
author_facet Mozhdeh Zamani
Sanaz Dastghaib
Mehran Erfani
Seyed Vahid Hosseini
Pooneh Mokarram
author_sort Mozhdeh Zamani
title The Role of endoplasmic reticulum metallo protease 1 on Autophagy Pathway in HCT-116 Colorectal Cancer Cell Line
title_short The Role of endoplasmic reticulum metallo protease 1 on Autophagy Pathway in HCT-116 Colorectal Cancer Cell Line
title_full The Role of endoplasmic reticulum metallo protease 1 on Autophagy Pathway in HCT-116 Colorectal Cancer Cell Line
title_fullStr The Role of endoplasmic reticulum metallo protease 1 on Autophagy Pathway in HCT-116 Colorectal Cancer Cell Line
title_full_unstemmed The Role of endoplasmic reticulum metallo protease 1 on Autophagy Pathway in HCT-116 Colorectal Cancer Cell Line
title_sort role of endoplasmic reticulum metallo protease 1 on autophagy pathway in hct-116 colorectal cancer cell line
publisher Shiraz University of Medical Sciences
publishDate 2021
url https://doaj.org/article/bd64c61cae1f425e9236a4357b5b8a24
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