Unraveling The Interplay Between Sterol Regulatory Element-Binding Protein 1 (SREBP-1) And The Lipophagy Receptor Oxysterol-Binding Protein-Related Protein 8 (ORP8) In Colorectal Carcinoma

Ayad, Nada Hashem; Eltokhy, Amira K.; Abo Safia, Hend S.; Abdallah, Hanan Mostafa Ismail; Dwidar, Amany Mohamed; Sultan, Weaam Ahmed; Elkasrawy, Kariman Helmy; Ibrahim, Hoda Ali Mohammed

doi:10.21608/ejhm.2025.424798.1841

Unraveling The Interplay Between Sterol Regulatory Element-Binding Protein 1 (SREBP-1) And The Lipophagy Receptor Oxysterol-Binding Protein-Related Protein 8 (ORP8) In Colorectal Carcinoma

Document Type : Original Article

Authors

¹ Biochemistry,Faculty of Medicine,Tanta University,Tanta,Egypt

² Medical Biochemistry & Molecular Biology Department,Faculty of Medicine, Tanta University, Egypt.

³ Pathology Department ,Faculty of Medicine, Tanta University ,Tanta, Egypt. Pathology Department of Basic Medical Sciences, Faculty of Medicine, Ibn Sina University For Medical Sciences. Amman 16197, Jordan.

⁴ Physiology Department,Faculty of Medicine,Tanta University,Tanta,Egypt

⁵ Gastroenterology and Hepatology, Internal Medicine Department, Faculty of Medicine, Tanta University, Egypt.

⁶ Human Anatomy and Embryology Department,Faculty of Medicine,Tanta University,Egypt.

⁷ Tropical Medicine and Infectious Diseases Department ,Faculty of Medicine, Tanta University , Tanta, Egypt.

⁸ Medical Biochemistry &Molecular Biology Department, Faculty of Medicine, Tanta University, Egypt.

10.21608/ejhm.2025.424798.1841

Abstract

Background: Autophagy is a cellular self-degradation process. Lipophagy is a selective autophagy of lipid droplets. Colorectal carcinoma has high incidence worldwide. Both sterol regulatory element-binding protein 1 (SREBP-1) and lipophagy participate in maintaining lipid homeostasis during tumor growth. Oxysterol-Binding Protein-Related Protein 8 acts as a lipophagy receptor, which interacts with microtubule-associated protein 1 light chain 3, and gamma-aminobutyric acid type A receptor-associated protein (LC3/GABARAPs). Autophagy may affect chronic inflammation and oxidative stress. Objective: This study aimed to elucidate the interplay between SREBP-1 and the lipophagy receptor oxysterol-binding protein-related protein 8 (ORP8) in colorectal carcinoma and their potential contribution in disease pathogenesis.
Patients and methods: The study comprised 12 colorectal carcinoma patients, enrolled into two groups: Group 1 (having the tumor specimens), and group 2 (having their corresponding safety margin specimens). The levels of interleukin 4 (IL-4), interleukin 6 (IL-6), malondialdehyde (MDA), LC3, catalase activity, gene expression levels of SREBP-1, ORP8, and GABARAP together with immunohistochemical expression of beclin-1 were determined.
Results: The current research displayed elevated gene expression levels of SREBP-1, immunohistochemical expression level of beclin 1, and protein levels of IL-4, IL-6, LC3, and MDA. Gene expression levels of ORP8, GABARAP, and catalase activity showed downregulation. There was negative relationship between SREBP-1 and ORP8 in colorectal carcinoma. Conclusion: SREBP-1 and ORP8 might contribute in disease pathogenesis.

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