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Epigenetic Regulation of Autophagy in Gastrointestinal Cancers Publisher Pubmed



Ghavami S1, 2, 3, 4 ; Zamani M2 ; Ahmadi M5 ; Erfani M6 ; Dastghaib S2, 7 ; Darbandi M8, 9 ; Darbandi S8, 9 ; Vakili O10 ; Siri M2 ; Grabarek BO11, 12 ; Boron D11, 12 ; Zarghooni M13 ; Wiechec E14 ; Mokarram P2, 15
Authors
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Authors Affiliations
  1. 1. Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada
  2. 2. Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  3. 3. Research Institute of Hematology and Oncology, Cancer Care Manitoba, Winnipeg, R3E 0V9, MB, Canada
  4. 4. Faculty of Medicine in Zabrze, University of Technology in Katowice, Academia of Silesia, Zabrze, 41-800, Poland
  5. 5. Department of Analytical Chemistry, Faculty of Chemistry, Bu-Ali Sina University, Hamedan, Iran
  6. 6. Department of Biochemistry, School of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
  7. 7. Endocrinology and Metabolism Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  8. 8. Fetal Health Research Center, Hope Generation Foundation, Tehran, Iran
  9. 9. Gene Therapy and Regenerative Medicine Research Center, Hope Generation Foundation, Tehran, Iran
  10. 10. Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
  11. 11. Department of Histology, Cytophysiology, and Embryology in Zabrze, Faculty of Medicine in Zabrze, University of Technology in Katowice, Academia of Silesia, Zabrze, 41-800, Poland
  12. 12. Department of Gynecology and Obstetrics in Zabrze, Faculty of Medicine in Zabrze, University of Technology in Katowice, Academia of Silesia, Zabrze, 41-800, Poland
  13. 13. Department of Laboratory Medicine and Pathobiology, University of Toronto Alumni, Toronto, Canada
  14. 14. Division of Cell Biology, Department of Biomedical and Clinical Sciences, Linkoping University, Linkoping, 58185, Sweden
  15. 15. Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

Source: Biochimica et Biophysica Acta - Molecular Basis of Disease Published:2022


Abstract

The development of novel therapeutic approaches is necessary to manage gastrointestinal cancers (GICs). Considering the effective molecular mechanisms involved in tumor growth, the therapeutic response is pivotal in this process. Autophagy is a highly conserved catabolic process that acts as a double-edged sword in tumorigenesis and tumor inhibition in a context-dependent manner. Depending on the stage of malignancy and cellular origin of the tumor, autophagy might result in cancer cell survival or death during the GICs' progression. Moreover, autophagy can prevent the progression of GIC in the early stages but leads to chemoresistance in advanced stages. Therefore, targeting specific arms of autophagy could be a promising strategy in the prevention of chemoresistance and treatment of GIC. It has been revealed that autophagy is a cytoplasmic event that is subject to transcriptional and epigenetic regulation inside the nucleus. The effect of epigenetic regulation (including DNA methylation, histone modification, and expression of non-coding RNAs (ncRNAs) in cellular fate is still not completely understood. Recent findings have indicated that epigenetic alterations can modify several genes and modulators, eventually leading to inhibition or promotion of autophagy in different cancer stages, and mediating chemoresistance or chemosensitivity. The current review focuses on the links between autophagy and epigenetics in GICs and discusses: 1) How autophagy and epigenetics are linked in GICs, by considering different epigenetic mechanisms; 2) how epigenetics may be involved in the alteration of cancer-related phenotypes, including cell proliferation, invasion, and migration; and 3) how epidrugs modulate autophagy in GICs to overcome chemoresistance. © 2022 Elsevier B.V.
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