ArticleClinical epigenetics2018
Epigenetic silencing of TMEM176A activates ERK signaling in human hepatocellular carcinoma.
Article in Clinical epigenetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Epigenetic silencingCancer biology & therapy · 2026Article
- TMEM72 Inhibits the proliferation by promoting cellular senescence through the activation of the P38/MAPK signaling pathway in renal cell carcinoma.Translational oncology · 2026Article
- Research progress on TMEM proteins in cancer progression and chemoresistance (Review).International journal of molecular medicine · 2025Review
- Lnc5q21.2, a novel long intergenic RNA, sensitizes colorectal cancer cells to ATR inhibitor by activating Wnt pathway.Journal of translational internal medicine · 2025Article
- The emerging role of transmembrane proteins in tumorigenesis and therapy.Translational cancer research · 2025Review
- Overexpression of PLCG2 and TMEM38A inhibit tumor progression in clear cell renal cell carcinoma.Scientific reports · 2025Article
- Epigenetic silencingCancer biology & therapy · 2024Article
- SAR1A Induces Cell Growth and Epithelial-Mesenchymal Transition Through the PI3K/AKT/mTOR Pathway in Head and Neck Squamous Cell Carcinoma: An In Vitro and In Vivo Study.Biomedicines · 2024Article
- TMEM205 induces TAM/M2 polarization to promote cisplatin resistance in gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024Article
- Epigenetic silencing of BEND4, a novel DNA damage repair gene, is a synthetic lethal marker for ATM inhibitor in pancreatic cancer.Frontiers of medicine · 2024Article
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- Immune checkpoints expression patterns in early-stage triple-negative breast cancer predict prognosis and remodel the tumor immune microenvironment.Frontiers in immunology · 2023Article
- Illustrating the biological functions and diagnostic value of transmembrane protein family members in glioma.Frontiers in oncology · 2023Article
- DNA methyltransferase-1 in acute myeloid leukaemia: beyond the maintenance of DNA methylation.Annals of medicine · 2022Review
- An in silico comparative transcriptome analysis identifying hub lncRNAs and mRNAs in brain metastatic small cell lung cancer (SCLC).Scientific reports · 2022Article
- Identifying Hub Genes and Immune Cell Infiltration for the Progression of Carotid Atherosclerotic Plaques in the Context of Predictive and Preventive Using Integrative Bioinformatics Approaches and Machine-Learning Strategies.Journal of immunology research · 2022Article
- Mechanisms of DNA Methylation in Virus-Host Interaction in Hepatitis B Infection: Pathogenesis and Oncogenetic Properties.International journal of molecular sciences · 2021Review
- LncRNA-URHC Functions as ceRNA to Regulate DNAJB9 Expression by Competitively Binding to miR-5007-3p in Hepatocellular Carcinoma.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Roles, molecular mechanisms, and signaling pathways of TMEMs in neurological diseases.American journal of translational research · 2021Review
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe role of TMEM176A in human hepatocellular carcinoma (HCC) is unknown. This study explored the epigenetic regulation and function of TMEM176A in human HCC. MATERIALS AND
methodsTwelve HCC cell lines and 126 cases of primary cancer were analyzed. Methylation-specific PCR, immunohistochemistry, flow cytometry, and xenograft mouse models were employed.
resultsTMEM176A was highly expressed in SNU387, SNU182, Huh1, and SNU475 cells; reduced expression was observed in HepG2 and PLC/PRF/5 cells; and no expression was found in SNU449, HBXF344, SMMC7721, Huh7, and LM3 cells. Unmethylation of the TMEM176A promoter was detected in SNU387, SNU182, Huh1, and SNU475 cells; partial methylation was observed in HepG2 and PLC/PRF/5 cells; and complete methylation was found in SNU449, HBXF344, SMMC7721, Huh7, and LM3 cells. Upon treatment with 5-Aza-2-deoxycytidine, re-expression of TMEM176A was detected in SNU449, HBXF344, SMMC7721, Huh7, and LM3 cells; increased expression of TMEM176A was observed in HepG2 and PLC/PRF/5 cells; and no expression changes were found in SNU387, SNU182, Huh1, and SNU475 cells. The TMEM176A promoter region was methylated in 75.4% (95/126) of primary human HCC. Reduced expression of TMEM176A was associated with promoter region methylation (P < 0.05). No association was found between TMEM176A promoter methylation and age, gender, HBV infection, liver cirrhosis, tumor size, lymph node metastasis, vessel cancerous embolus, number of lesions, and TNM stage (all P > 0.05). These results demonstrated that the expression of TMEM176A is regulated by promoter region methylation. Methylation of the TMEM176A promoter was significantly associated with tumor cell differentiation (P < 0.05) and was an independent prognostic factor for poor 3-year overall survival (OS, P < 0.05). TMEM176A expression induced cell apoptosis; inhibited cell proliferation, migration, and invasion; suppressed human HCC cell xenograft growth in mice; and inhibited ERK signaling in HCC cells.
conclusionThe promoter region of TMEM176A is frequently methylated in human HCC, and the expression of TMEM176A is regulated by promoter region methylation. Methylation of the TMEM176A promoter may serve as a diagnostic and prognostic marker in HCC. TMEM176A suppresses HCC growth by inhibiting the ERK signaling pathway.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.