ArticleCellular and molecular gastroenterology and hepatology2023
Identification of a Transmembrane Protein Involved in Shear Stress Signaling and Hepatocarcinogenesis After a Sustained Virological Response to Hepatitis C Virus.
Article in Cellular and molecular gastroenterology and hepatology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 7 citations in OpenAlex.
- HCV-Induced Hepatocarcinogenesis: Molecular Mechanisms, Persistent Cancer Risk, and Future Perspectives.Biomedicines · 2026Review
- Vessels encapsulating tumor clusters in hepatocellular carcinoma: a distinct metastatic pathway with diagnostic and therapeutic significance.Journal of translational medicine · 2026Review
- Cryo-EM structure of TMEM164 reveals distinct phospholipid remodeling mechanisms with anti-ferroptotic potential.Nature communications · 2025Article
- Research Progress on the Role of Epigenetic Methylation Modification in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2024Review
- Memories of Stress: The Imprinted Cancer Risk After HCV Cure.Cellular and molecular gastroenterology and hepatology · 2023Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsThe risk of hepatocellular carcinoma (HCC) remains after achieving a sustained virological response (SVR) in patients with chronic hepatitis C (CHC). Epigenetic abnormalities might be key regulators in the development of HCC. This study aimed to identify the genes involved in hepatocarcinogenesis after an SVR.
methodsDNA methylation in liver tissue was compared between 21 CHC patients without HCC and 28 CHC patients with HCC, all of whom had achieved an SVR. Additional comparisons with 23 CHC patients before treatment and 10 normal livers were performed. The characteristics of a newly identified gene were explored in vitro and in vivo.
resultsWe found that the transmembrane protein no. 164 (TMEM164) gene was demethylated by hepatitis C virus infection and HCC development after achieving an SVR. TMEM164 was expressed mainly in endothelial cells, alpha smooth muscle actin-positive cells, and some capillarized liver sinusoidal endothelial cells. TMEM164 expression was significantly correlated with liver fibrosis and relapse-free survival in HCC patients. TMEM164 was induced by shear stress, interacted with GRP78/BiP, accelerated ATF6 (activating transcription factor 6)-mediated endoplasmic reticulum (ER) stress signaling, and activated interleukin-6/STAT3 (signal transducer and activator of transcription 3) signaling in the TMNK1 liver endothelial cell line. Therefore, we termed TMEM164 "shear stress-induced transmembrane protein associated with ER stress signaling" (SHERMER). SHERMER knockout mice were protected against CCL4-induced liver fibrosis. SHERMER overexpression in TMNK1 cells accelerated HCC growth in a xenograft model.
conclusionsWe identified a new transmembrane protein, SHERMER, in CHC patients with HCC after achieving an SVR. SHERMER was induced by shear stress and accelerated ATF6-mediated ER stress signaling in endothelial cells. Thus, SHERMER is a novel endothelial marker associated with liver fibrosis, hepatocarcinogenesis, and progression of HCC.
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