{"title":"Precision Chemotherapy in Biliary Tract Cancer moving From Empiric Intensification to Biomarker-Guided Treatment: Editorial on \"Molecular determinants of outcome to gemcitabine, cisplatin, and nab-paclitaxel in patients with advanced BTC.\"","authors":"Sung Hwan Lee, Ahmed O Kaseb, Ju-Seog Lee","doi":"10.3350/cmh.2026.0179","DOIUrl":"https://doi.org/10.3350/cmh.2026.0179","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lohitesh Kovooru, Jingjing Zhang, Francesco Giuseppe Monni, Tanmoy Dutta, Xiangdong Gongye, Bernice Asiedu, Patrizia Infelise, Emelie Barreby, Oveis Jamialahmadi, Margit Mahlapuu, Rosellina M Mancina, Stefano Romeo
Background & aims: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide and is driven by metabolic reprogramming that supports tumor growth and progression. A common missense genetic variant (rs2642438, p.A165T) in Mitochondrial amidoxime reducing component 1 (MTARC1), identified as protective against liver disease, has been recently associated with lower prevalence of steatosis, cirrhosis, and HCC. However, the mechanistic role of MTARC1 in HCC is unclear. Therefore, we sought to decipher the role of MTARC1 in HCC.
Methods: We investigated the role of MTARC1 in HCC by performing siRNA-mediated knockdown across human immortalized HCC cell lines (Hep3B2, HuH7, HepG2 and HepaRG) homozygous for the risk allele (p.A165) and by generating stable CRISPR-Cas9 knockout (KO) models. Next, we assessed the effect of MTARC1 loss on cell proliferation, migration, lipid metabolism, and fatty acid oxidation in vitro, as well as tumor aggressiveness in a subcutaneous xenograft mouse model. Additionally, we performed global proteomics in both in vitro and xenograft models.
Results: Transient knockdown of MTARC1 p.A165 reduced proliferation in HCC cell lines. CRISPR-Cas9-mediated stable MTARC1 p.A165 KO in Hep3B2 cells led to decreased neutral lipid intracellular accumulation, enhanced β-oxidation and reduced cell migration. A MTARC1 KO xenograft model had reduced tumor volume . Proteomic analyses of both in vitro HCC cells and xenograft tumors revealed inhibition of oncogenic pathways and activation of anti-proliferative proteins.
Conclusions: Downregulation of MTARC1 p.A165 inhibits lipid accumulation, dampens tumor-promoting pathways and restricts tumor growth, highlighting MTARC1 as a promising therapeutic target for HCC.
{"title":"MTARC1 p.A165 ablation reduces hepatocellular carcinoma aggressiveness in vitro and in vivo.","authors":"Lohitesh Kovooru, Jingjing Zhang, Francesco Giuseppe Monni, Tanmoy Dutta, Xiangdong Gongye, Bernice Asiedu, Patrizia Infelise, Emelie Barreby, Oveis Jamialahmadi, Margit Mahlapuu, Rosellina M Mancina, Stefano Romeo","doi":"10.3350/cmh.2025.1261","DOIUrl":"https://doi.org/10.3350/cmh.2025.1261","url":null,"abstract":"<p><strong>Background & aims: </strong>Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide and is driven by metabolic reprogramming that supports tumor growth and progression. A common missense genetic variant (rs2642438, p.A165T) in Mitochondrial amidoxime reducing component 1 (MTARC1), identified as protective against liver disease, has been recently associated with lower prevalence of steatosis, cirrhosis, and HCC. However, the mechanistic role of MTARC1 in HCC is unclear. Therefore, we sought to decipher the role of MTARC1 in HCC.</p><p><strong>Methods: </strong>We investigated the role of MTARC1 in HCC by performing siRNA-mediated knockdown across human immortalized HCC cell lines (Hep3B2, HuH7, HepG2 and HepaRG) homozygous for the risk allele (p.A165) and by generating stable CRISPR-Cas9 knockout (KO) models. Next, we assessed the effect of MTARC1 loss on cell proliferation, migration, lipid metabolism, and fatty acid oxidation in vitro, as well as tumor aggressiveness in a subcutaneous xenograft mouse model. Additionally, we performed global proteomics in both in vitro and xenograft models.</p><p><strong>Results: </strong>Transient knockdown of MTARC1 p.A165 reduced proliferation in HCC cell lines. CRISPR-Cas9-mediated stable MTARC1 p.A165 KO in Hep3B2 cells led to decreased neutral lipid intracellular accumulation, enhanced β-oxidation and reduced cell migration. A MTARC1 KO xenograft model had reduced tumor volume . Proteomic analyses of both in vitro HCC cells and xenograft tumors revealed inhibition of oncogenic pathways and activation of anti-proliferative proteins.</p><p><strong>Conclusions: </strong>Downregulation of MTARC1 p.A165 inhibits lipid accumulation, dampens tumor-promoting pathways and restricts tumor growth, highlighting MTARC1 as a promising therapeutic target for HCC.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reply to Correspondence: Advancing Immune-Informed and Subgroup-Stratified Research on the MET-TRIB3 Axis.","authors":"Lei Wu, Yan Zheng","doi":"10.3350/cmh.2026.0131","DOIUrl":"https://doi.org/10.3350/cmh.2026.0131","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correspondence: Response to Editorial on \"Extending MET-TRIB3 Axis Research in Hepatocellular Carcinoma: Immune Contexture and Patient Subgroups\".","authors":"Tiantian Wang, Wenjie Huang, Limin Xia","doi":"10.3350/cmh.2026.0088","DOIUrl":"https://doi.org/10.3350/cmh.2026.0088","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reply to \"A Call for More Efforts to Incorporate Liver in the Metabolic Health Framework\".","authors":"Shadi Zerehpoosh, Ziyan Pan, Mohammed Eslam","doi":"10.3350/cmh.2026.0133","DOIUrl":"https://doi.org/10.3350/cmh.2026.0133","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Critical Considerations on the Study of Normal-Weight MASLD Across Diverse Populations.","authors":"Qingshang Li, Xiaona Hu, Yuanwen Chen, Zhijun Bao","doi":"10.3350/cmh.2026.0067","DOIUrl":"https://doi.org/10.3350/cmh.2026.0067","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brian P Lee, Christopher Scannell, Matt Dukewich, Jennifer L Dodge, Norah A Terrault, Dima Mazen Qato
{"title":"National Trends in Resmetirom Prescriptions for Metabolic Dysfunction-Associated Steatohepatitis in the USA.","authors":"Brian P Lee, Christopher Scannell, Matt Dukewich, Jennifer L Dodge, Norah A Terrault, Dima Mazen Qato","doi":"10.3350/cmh.2025.1414","DOIUrl":"https://doi.org/10.3350/cmh.2025.1414","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Taeeung Kim, Le Bich Hang Pham, Jeeyeon Lee, Keon Wook Kang
{"title":"Correspondence to editorial on \"A New Lens on Ferroptosis in Liver Disease: Near-Infrared Fluorescent Probe of Lipid Peroxidation-Driven Microenvironmental Remodeling\" and \"Mapping Lipid Droplet Viscosity: A Novel Tool for Spatiotemporal Ferroptosis\".","authors":"Taeeung Kim, Le Bich Hang Pham, Jeeyeon Lee, Keon Wook Kang","doi":"10.3350/cmh.2026.0094","DOIUrl":"https://doi.org/10.3350/cmh.2026.0094","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sherlot Juan Song, Terry Cheuk-Fung Yip, Vincent Wai-Sun Wong, Dae Won Jun
{"title":"The Lean Phenotype in Metabolic Dysfunction-associated Steatotic Liver Disease: Diagnostic Challenges and Prognostic Implications.","authors":"Sherlot Juan Song, Terry Cheuk-Fung Yip, Vincent Wai-Sun Wong, Dae Won Jun","doi":"10.3350/cmh.2026.0143","DOIUrl":"https://doi.org/10.3350/cmh.2026.0143","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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