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The DUBR/miR-210-5p/RETSAT Axis in Cholesterol-Associated Steatohepatitis: Clinical Signatures and Molecular Mechanisms
Metabolic-associated fatty liver disease (MAFLD) represents an increasing global health challenge, with cholesterol-associated steatohepatitis (CASH) emerging as a distinct pathological entity warranting investigation. While CASH demonstrates unique features compared to traditional triglyceride-driv...
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2025
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| _version_ | 1867613425311416320 |
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| access_status_str | Open Access |
| author | Mahmoud Abdelzaher, Hana |
| author_browse | Mahmoud Abdelzaher, Hana |
| author_facet | Mahmoud Abdelzaher, Hana |
| author_sort | Mahmoud Abdelzaher, Hana |
| collection | Thesis |
| description | Metabolic-associated fatty liver disease (MAFLD) represents an increasing global health challenge, with cholesterol-associated steatohepatitis (CASH) emerging as a distinct pathological entity warranting investigation. While CASH demonstrates unique features compared to traditional triglyceride-driven steatohepatitis, its underlying molecular mechanisms remain poorly understood. This study investigates a novel regulatory axis involving DPPA2 Upstream Binding RNA (DUBR), miR-210-5p, and retinol saturase (RETSAT). 170 patient samples revealed progressive axis dysregulation in disease states, with RETSAT emerging as a highly accurate diagnostic marker (AUC=1.000). Using novel in vitro models of MASH and CASH, we demonstrated that miR-210-5p modulation significantly affects lipid accumulation and cellular phenotype, with more pronounced effects in cholesterol-rich environments. Mechanistic studies revealed that miR-210-5p inhibition dramatically increased lipid accumulation and altered the expression of key metabolic regulators, suggesting its role as a metabolic mediator rather than the master regulator. These findings identify new molecular mechanisms in CASH pathogenesis, establish RETSAT as a potential diagnostic biomarker, and reveal promising therapeutic targets for intervention. |
| format | Thesis |
| id | oai:fount.aucegypt.edu:etds-3588 |
| institution | American University in Cairo (Egypt) |
| last_indexed | 2026-06-10T12:35:56.457Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from AUC Knowledge Fountain — bepress |
| publishDate | 2025 |
| publishDateRange | 2025 |
| publishDateSort | 2025 |
| publisher | AUC Knowledge Fountain |
| publisherStr | AUC Knowledge Fountain |
| record_format | dspace |
| source_str | AUC Knowledge Fountain — bepress |
| spelling | oai:fount.aucegypt.edu:etds-3588 The DUBR/miR-210-5p/RETSAT Axis in Cholesterol-Associated Steatohepatitis: Clinical Signatures and Molecular Mechanisms Mahmoud Abdelzaher, Hana Metabolic-associated fatty liver disease (MAFLD) represents an increasing global health challenge, with cholesterol-associated steatohepatitis (CASH) emerging as a distinct pathological entity warranting investigation. While CASH demonstrates unique features compared to traditional triglyceride-driven steatohepatitis, its underlying molecular mechanisms remain poorly understood. This study investigates a novel regulatory axis involving DPPA2 Upstream Binding RNA (DUBR), miR-210-5p, and retinol saturase (RETSAT). 170 patient samples revealed progressive axis dysregulation in disease states, with RETSAT emerging as a highly accurate diagnostic marker (AUC=1.000). Using novel in vitro models of MASH and CASH, we demonstrated that miR-210-5p modulation significantly affects lipid accumulation and cellular phenotype, with more pronounced effects in cholesterol-rich environments. Mechanistic studies revealed that miR-210-5p inhibition dramatically increased lipid accumulation and altered the expression of key metabolic regulators, suggesting its role as a metabolic mediator rather than the master regulator. These findings identify new molecular mechanisms in CASH pathogenesis, establish RETSAT as a potential diagnostic biomarker, and reveal promising therapeutic targets for intervention. 2025-06-15T07:00:00Z thesis application/pdf https://fount.aucegypt.edu/etds/2539 https://fount.aucegypt.edu/context/etds/article/3588/viewcontent/Hana_Mahmoud_Thesis.pdf Theses and Dissertations AUC Knowledge Fountain Cholesterol-associated steatohepatitis; MAFLD; DUBR; miR-210-5p; RETSAT; Biomarkers Diagnosis Therapeutics |
| spellingShingle | Cholesterol-associated steatohepatitis; MAFLD; DUBR; miR-210-5p; RETSAT; Biomarkers Diagnosis Therapeutics Mahmoud Abdelzaher, Hana The DUBR/miR-210-5p/RETSAT Axis in Cholesterol-Associated Steatohepatitis: Clinical Signatures and Molecular Mechanisms |
| title | The DUBR/miR-210-5p/RETSAT Axis in Cholesterol-Associated Steatohepatitis: Clinical Signatures and Molecular Mechanisms |
| title_full | The DUBR/miR-210-5p/RETSAT Axis in Cholesterol-Associated Steatohepatitis: Clinical Signatures and Molecular Mechanisms |
| title_fullStr | The DUBR/miR-210-5p/RETSAT Axis in Cholesterol-Associated Steatohepatitis: Clinical Signatures and Molecular Mechanisms |
| title_full_unstemmed | The DUBR/miR-210-5p/RETSAT Axis in Cholesterol-Associated Steatohepatitis: Clinical Signatures and Molecular Mechanisms |
| title_short | The DUBR/miR-210-5p/RETSAT Axis in Cholesterol-Associated Steatohepatitis: Clinical Signatures and Molecular Mechanisms |
| title_sort | dubr mir 210 5p retsat axis in cholesterol associated steatohepatitis clinical signatures and molecular mechanisms |
| topic | Cholesterol-associated steatohepatitis; MAFLD; DUBR; miR-210-5p; RETSAT; Biomarkers Diagnosis Therapeutics |
| url | https://fount.aucegypt.edu/etds/2539 https://fount.aucegypt.edu/context/etds/article/3588/viewcontent/Hana_Mahmoud_Thesis.pdf |
| work_keys_str_mv | AT mahmoudabdelzaherhana thedubrmir2105pretsataxisincholesterolassociatedsteatohepatitisclinicalsignaturesandmolecularmechanisms AT mahmoudabdelzaherhana dubrmir2105pretsataxisincholesterolassociatedsteatohepatitisclinicalsignaturesandmolecularmechanisms |