Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Novel role of general transcript factor IIH subunit 2 (GTF2H2) in the development and sex disparity of hepatocellular carcinoma

Oncogene volume 44, pages 1323–1335 (2025)Cite this article

Subjects

Abstract

Sex disparity is a hepatocellular carcinoma (HCC) hallmark, demonstrating aggressiveness and mortality more frequently in men than in women. However, the components of its basis remain largely unknown. It was identified in HCC frequent loss of heterozygosity of general transcript factor IIH subunit 2 (GTF2H2), a potential estrogen pathway gene. GTF2H2 functions in nucleotide excision repair (NER) and basal transcription, but the function of GTF2H2 in cancer has not been described in depth. Here, it was identified that GTF2H2 inhibited growth and invasive mobility and induced apoptosis of HCC cells, which was up-regulated by estrogen-dependent estrogen receptor alpha (ERα) signaling. Mechanistically, in vitro estrogen-treated HCC models with GTF2H2 knockdown and over-expression showed estrogen-regulated GTF2H2 promoted NER of HCC genomic DNA and inhibited cell cycle progression, and down-regulated PAM/NF-κB pathway. Xenografted HCC mice models showed higher tumor progression of HCC with low GTF2H2 expression in ovariectomized female mice or male mice, but could be rescued by GTF2H2 over-expression, which was also observed in spontaneous tumor mice models. Clinical association analysis of HCC cases showed GTF2H2 expression was higher in female HCC, with correlation positively with ERα expression. Taken together, the estrogen-regulated GTF2H2 may be involved in the development and sex disparity of HCC by maintaining NER-related genomic stability and affecting PAM/NF-κB signaling pathway.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: GTF2H2 was regulated by estrogen-dependent ERα signaling and affected the behavior of HCC cells.
Fig. 2: Higher tumor progression was observed in male xenografted tumor mice and male spontaneous liver tumor mice with lower GTF2H2 expression.
Fig. 3: GTF2H2-mediated estrogen regulation on cell cycle progression and NER of HCC genomic DNA.
Fig. 4: GTF2H2 could modulate estrogen-related PAM/NF-κB pathway involved in progression of HCC.
Fig. 5: GTF2H2 expression was decreased in human HCC tumor tissue and positively correlated with ERα expression.

Similar content being viewed by others

Data availability

All data generated or analyzed during this study are basically included in this published article (and its supplementary information files).

References

  1. Rich NE. Changing Epidemiology of Hepatocellular Carcinoma Within the United States and Worldwide. Surg Oncol Clin N. Am. 2024;33:1–12.

    Article  PubMed  Google Scholar 

  2. Yue T, Xu M, Cai T, Zhu H, Pourkarim MR, De Clercq E, et al. Gender disparity and temporal trend of liver cancer in China from 1990 to 2019 and predictions in a 25-year period. Front Public Health. 2022;10:956712.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Haupt S, Caramia F, Klein SL, Rubin JB, Haupt Y. Sex disparities matter in cancer development and therapy. Nat Rev Cancer. 2021;21:393–407.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Toniutto P, Shalaby S, Mameli L, Morisco F, Gambato M, Cossiga V, et al. Role of sex in liver tumor occurrence and clinical outcomes: A comprehensive review. Hepatology. 2024;79:1141–57.

    Article  PubMed  Google Scholar 

  5. Li Y, Xu A, Jia S, Huang J. Recent advances in the molecular mechanism of sex disparity in hepatocellular carcinoma. Oncol Lett. 2019;17:4222–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Yun J, Kim YS, Heo MJ, Kim MJ, Moon A, Kim SG. ERalpha inhibits mesenchymal and amoeboidal movement of liver cancer cell via Galpha12. Int J Cancer. 2022;150:1690–705.

    Article  CAS  PubMed  Google Scholar 

  7. Lu Y, Tian N, Hu L, Meng J, Feng M, Zhu Y, et al. ERalpha down-regulates carbohydrate responsive element binding protein and decreases aerobic glycolysis in liver cancer cells. J Cell Mol Med. 2021;25:3427–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Jiang M, Jia K, Wang L, Li W, Chen B, Liu Y, et al. Alterations of DNA damage response pathway: Biomarker and therapeutic strategy for cancer immunotherapy. Acta Pharm Sin B. 2021;11:2983–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Pasqui A, Boddi A, Campanacci DA, Scoccianti G, Bernini A, Grasso D, et al. Alteration of the Nucleotide Excision Repair (NER) Pathway in Soft Tissue Sarcoma. Int J Mol Sci. 2022;23:8360.

  10. Zhao Z, Chen GY, Long J, Li H, Huang J. Genomic losses at 5q13.2 and 8p23.1 in dysplastic hepatocytes are common events in hepatitis B virus-related hepatocellular carcinoma. Oncol Lett. 2015;9:2839–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Johannsdottir HK, Jonsson G, Johannesdottir G, Agnarsson BA, Eerola H, Arason A, et al. Chromosome 5 imbalance mapping in breast tumors from BRCA1 and BRCA2 mutation carriers and sporadic breast tumors. Int J Cancer. 2006;119:1052–60.

    Article  CAS  PubMed  Google Scholar 

  12. Walker LC, Marquart L, Pearson JF, Wiggins GA, O’Mara TA, Parsons MT, et al. Evaluation of copy-number variants as modifiers of breast and ovarian cancer risk for BRCA1 pathogenic variant carriers. Eur J Hum Genet. 2017;25:432–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ouyang Q, Li YM, Xu AJ, Zhou DH, Li ZK, Huang J, et al. GTF2H2 affects the proliferation and migration of Hep3B hepatocellular carcinoma cells by mediating AKT signal pathway. China Biotechnol 2021;41:4–12.

    CAS  Google Scholar 

  14. Li Z, Li Y, Ouyang Q, Li X, Huang J. Exosome-derived GTF2H2 from Huh7 cells can inhibit endothelial cell viability, migration, tube formation, and permeability. Tissue Cell. 2022;79:101922.

    Article  CAS  PubMed  Google Scholar 

  15. Markaverich BM, Shoulars K, Rodriguez MA. Luteolin Regulation of Estrogen Signaling and Cell Cycle Pathway Genes in MCF-7 Human Breast Cancer Cells. Int J Biomed Sci. 2011;7:101–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Cicatiello L, Scafoglio C, Altucci L, Cancemi M, Natoli G, Facchiano A, et al. A genomic view of estrogen actions in human breast cancer cells by expression profiling of the hormone-responsive transcriptome. J Mol Endocrinol. 2004;32:719–75.

    Article  CAS  PubMed  Google Scholar 

  17. Humbert S, van Vuuren H, Lutz Y, Hoeijmakers JH, Egly JM, Moncollin V. p44 and p34 subunits of the BTF2/TFIIH transcription factor have homologies with SSL1, a yeast protein involved in DNA repair. EMBO J. 1994;13:2393–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kim J, Li CL, Chen X, Cui Y, Golebiowski FM, Wang H, et al. Lesion recognition by XPC, TFIIH and XPA in DNA excision repair. Nature. 2023;617:170–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Nieto Moreno N, Olthof AM, Svejstrup JQ. Transcription-Coupled Nucleotide Excision Repair and the Transcriptional Response to UV-Induced DNA Damage. Annu Rev Biochem. 2023;92:81–113.

    Article  CAS  PubMed  Google Scholar 

  20. Kim Y, Jeong J, Lee S, Choi I, Choi J. Identification of adverse outcome pathway related to high-density polyethylene microplastics exposure: Caenorhabditis elegans transcription factor RNAi screening and zebrafish study. J Hazard Mater. 2020;388:121725.

    Article  CAS  PubMed  Google Scholar 

  21. Marchetti AL, Zhang H, Kim ES, Yu X, Jang S, Wang M, et al. Proteomic Analysis of Nuclear Hepatitis B Virus Relaxed Circular DNA-Associated Proteins Identifies UV-Damaged DNA Binding Protein as a Host Factor Involved in Covalently Closed Circular DNA Formation. J Virol. 2022;96:e0136021.

    Article  PubMed  Google Scholar 

  22. Chen YW, Tucker MD, Brown LC, Yasin HA, Ancell KK, Armstrong AJ, et al. The Association between a Decrease in On-Treatment Neutrophil-to-Eosinophil Ratio (NER) at Week 6 after Ipilimumab Plus Nivolumab Initiation and Improved Clinical Outcomes in Metastatic Renal Cell Carcinoma. Cancers (Basel). 2022;14:3830.

  23. Nairuz T, Rahman M, Bushra MU, Kabir Y. TP53 Arg72Pro and XPD Lys751Gln Gene Polymorphisms and Risk of Lung Cancer in Bangladeshi Patients. Asian Pac J Cancer Prev. 2020;21:2091–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Nairuz T, Bushra YU, Kabir Y. Effect of XPD and TP53 Gene Polymorphisms on the Risk of Platinum-Based Chemotherapy Induced Toxicity in Bangladeshi Lung Cancer Patients. Asian Pac J Cancer Prev. 2021;22:3809–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Kang TH. Circadian Rhythm of NER and ATR Pathways. Biomolecules. 2021;11:715.

  26. Garikapati K, Young IC, Hong S, Rai P, Jain C, Briegel KJ. Blocking LBH expression causes replication stress and sensitizes triple-negative breast cancer cells to ATR inhibitor treatment. Oncogene. 2024;43:851–65.

    Article  CAS  PubMed  Google Scholar 

  27. Wang WS, Chen YS, Kuo CY, Tsai JJ, Hsu FT, Chung JG, et al. DNA damage and NF-kappaB inactivation implicate glycyrrhizic acid-induced G(1) phase arrest in hepatocellular carcinoma cells. J Food Biochem. 2022;46:e14128.

    CAS  PubMed  Google Scholar 

  28. He Y, Pasupala N, Zhi H, Dorjbal B, Hussain I, Shih HM, et al. NF-kappaB-induced R-loop accumulation and DNA damage select for nucleotide excision repair deficiencies in adult T cell leukemia. Proc Natl Acad Sci USA. 2021;118:e2005568118.

  29. Singh R, Rajput M, Singh RP. Simulated microgravity triggers DNA damage and mitochondria-mediated apoptosis through ROS generation in human promyelocytic leukemic cells. Mitochondrion. 2021;61:114–24.

    Article  CAS  PubMed  Google Scholar 

  30. Nevola R, Tortorella G, Rosato V, Rinaldi L, Imbriani S, Perillo P, et al. Gender Differences in the Pathogenesis and Risk Factors of Hepatocellular Carcinoma. Biology (Basel). 2023;12:984.

  31. Yan LJ, Yao SY, Meng GX, Liu KX, Li HC, Ding ZN, et al. Sex and regional disparities in incidence of hepatocellular carcinoma in autoimmune hepatitis: a systematic review and meta-analysis. Hepatol Int. 2021;15:1413–20.

    Article  PubMed  Google Scholar 

  32. Plewinski P, Ksiazkiewicz M, Rychel-Bielska S, Rudy E, Wolko B. Candidate Domestication-Related Genes Revealed by Expression Quantitative Trait Loci Mapping of Narrow-Leafed Lupin (Lupinus angustifolius L.). Int J Mol Sci. 2019;20:5670.

  33. Kuper J, Kisker C. Three targets in one complex: A molecular perspective of TFIIH in cancer therapy. DNA Repair (Amst). 2021;105:103143.

    Article  CAS  PubMed  Google Scholar 

  34. Theil AF, Hackes D, Lans H. TFIIH central activity in nucleotide excision repair to prevent disease. DNA Repair (Amst). 2023;132:103568.

    Article  CAS  PubMed  Google Scholar 

  35. Yu J, Yan C, Dodd T, Tsai CL, Tainer JA, Tsutakawa SE, et al. Dynamic conformational switching underlies TFIIH function in transcription and DNA repair and impacts genetic diseases. Nat Commun. 2023;14:2758.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Chen P, Li B, Ou-Yang L. Role of estrogen receptors in health and disease. Front Endocrinol (Lausanne). 2022;13:839005.

    Article  PubMed  Google Scholar 

  37. Huang S, Wang W, Cheng Y, Lin J, Wang M. Clinicopathological and Prognostic Significance of Klotho and Estrogen Receptors Expression in Human Hepatocellular Carcinoma. Turk J Gastroenterol. 2021;32:828–36.

    Article  PubMed  PubMed Central  Google Scholar 

  38. O’Brien MH, Pitot HC, Chung SH, Lambert PF, Drinkwater NR, Bilger A. Estrogen Receptor-alpha Suppresses Liver Carcinogenesis and Establishes Sex-Specific Gene Expression. Cancers (Basel). 2021;13:2355.

  39. Mouw KW, D’Andrea AD, Konstantinopoulos PA. Nucleotide excision repair (NER) alterations as evolving biomarkers and therapeutic targets in epithelial cancers. Oncoscience. 2015;2:942–3.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Hirakawa M, Sato Y, Ohnuma H, Takayama T, Sagawa T, Nobuoka T, et al. A phase II study of neoadjuvant combination chemotherapy with docetaxel, cisplatin, and S-1 for locally advanced resectable gastric cancer: nucleotide excision repair (NER) as potential chemoresistance marker. Cancer Chemother Pharmacol. 2013;71:789–97.

    Article  CAS  PubMed  Google Scholar 

  41. Han P, Liu H, Shi Q, Liu Z, Troy JD, Lee WT, et al. Associations between expression levels of nucleotide excision repair proteins in lymphoblastoid cells and risk of squamous cell carcinoma of the head and neck. Mol Carcinog. 2018;57:784–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Zhang R, Zhou F, Cheng L, Yu A, Zhu M, Wang M, et al. Genetic variants in nucleotide excision repair pathway predict survival of esophageal squamous cell cancer patients receiving platinum-based chemotherapy. Mol Carcinog. 2018;57:1553–65.

    Article  CAS  PubMed  Google Scholar 

  43. Anand SK, Sharma A, Singh N, Kakkar P. Entrenching role of cell cycle checkpoints and autophagy for maintenance of genomic integrity. DNA Repair (Amst). 2020;86:102748.

    Article  CAS  PubMed  Google Scholar 

  44. Russo LC, Farias JO, Forti FL. DUSP3 maintains genomic stability and cell proliferation by modulating NER pathway and cell cycle regulatory proteins. Cell Cycle. 2020;19:1545–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Mahmoud AA, Hassan MH, Ghweil AA, Abdelrahman A, Mohammad AN, Ameen HH. Urinary 8-hydroxydeoxyguanosine in relation to XRCC1 rs25487 G/A (Arg399Gln) and OGG1 rs1052133 C/G (Ser326Cys) DNA repair genes polymorphisms in patients with chronic hepatitis C and related hepatocellular carcinoma. Cancer Manag Res. 2019;11:5343–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Yugawa K, Itoh S, Yoshizumi T, Yoshiya S, Takeishi K, Toshima T, et al. Prognostic impact of 8-hydroxy-deoxyguanosine and its repair enzyme 8-hydroxy-deoxyguanosine DNA glycosylase in hepatocellular carcinoma. Pathol Int. 2020;70:533–41.

    Article  CAS  PubMed  Google Scholar 

  47. Harris CM, Zamperoni KE, Sernoskie SC, Chow NSM, Massey TE. Effects of in vivo treatment of mice with sulforaphane on repair of DNA pyridyloxylbutylation. Toxicology. 2021;454:152753.

    Article  CAS  PubMed  Google Scholar 

  48. Martens MC, Emmert S, Boeckmann L. Xeroderma Pigmentosum: Gene Variants and Splice Variants. Genes (Basel). 2021;12:1173.

  49. Saha LK, Wakasugi M, Akter S, Prasad R, Wilson SH, Shimizu N, et al. Topoisomerase I-driven repair of UV-induced damage in NER-deficient cells. Proc Natl Acad Sci USA. 2020;117:14412–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Clusan L, Ferriere F, Flouriot G, Pakdel F. A Basic Review on Estrogen Receptor Signaling Pathways in Breast Cancer. Int J Mol Sci. 2023;24:6834.

  51. Hassan HA, Mohamed Abdelhamid A, Samy W, Osama Mohammed H, Mortada Mahmoud S, Fawzy Abdel Mageed A, et al. Ameliorative effects of androstenediol against acetic acid-induced colitis in male wistar rats via inhibiting TLR4-mediated PI3K/Akt and NF-kappaB pathways through estrogen receptor beta activation. Int Immunopharmacol. 2024;127:111414.

    Article  CAS  PubMed  Google Scholar 

  52. Glaviano A, Foo ASC, Lam HY, Yap KCH, Jacot W, Jones RH, et al. PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer. Mol Cancer. 2023;22:138.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Siraj MA, Jacobs AT, Tan GT. Altersolanol B, a fungal tetrahydroanthraquinone, inhibits the proliferation of estrogen receptor-expressing (ER+) human breast adenocarcinoma by modulating PI3K/AKT, p38/ERK MAPK and associated signaling pathways. Chem Biol Interact. 2022;359:109916.

    Article  CAS  PubMed  Google Scholar 

  54. Iyer JK, Kalra M, Kaul A, Payton ME, Kaul R. Estrogen receptor expression in chronic hepatitis C and hepatocellular carcinoma pathogenesis. World J Gastroenterol. 2017;23:6802–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Sukocheva OA. Estrogen, estrogen receptors, and hepatocellular carcinoma: Are we there yet? World J Gastroenterol. 2018;24:1–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Li Y, Xu A, Liu S, Zhang W, Zhou D, OuYang Q, et al. SUGP2 p.(Arg639Gln) variant is involved in the pathogenesis of hemochromatosis via the CIRBP/BMPER signaling pathway. Am J Hematol. 2024;99:1691–703.

Download references

Acknowledgements

The authors would like to thank Prof Run Song (Beijing Institute of Radiation Medicine) for kindly providing the UV radiation platform.

Funding

This study was supported by grants from the Nature Science Foundation of China (no. 81650014) and Beijing Natural Science Foundation (no. 7132058).

Author information

Author notes

  1. These authors contributed equally: Yanmeng Li, Qin Ouyang, Zhibin Chen.

Authors and Affiliations

  1. Laboratory of Molecular Biology, Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China

    Yanmeng Li, Qin Ouyang, Zhibin Chen, Donghu Zhou, Zhenkun Li, Xiaojin Li, Siyu Jia, Huaduan Zi, Saiping Qi, Hengcheng Tang, Bei Zhang, Anjian Xu & Jian Huang

  2. Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, Beijing, 100050, China

    Yanmeng Li & Jidong Jia

  3. National Clinical Research Center for Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, China

    Yanmeng Li, Qin Ouyang, Donghu Zhou, Zhenkun Li, Xiaojin Li, Siyu Jia, Huaduan Zi, Saiping Qi, Hengcheng Tang, Bei Zhang, Anjian Xu, Jidong Jia & Jian Huang

  4. Central Laboratory, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China

    Zhibin Chen

  5. Clinical Research Center, Beijing Children Hospital, Capital Medical University, Beijing, China

    Xiaoxi Yang

  6. Department of Oncology Minimally Invasive Interventional Radiology, Beijing You-an Hospital, Capital Medical University, Beijing, China

    Jiang Long

  7. Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing, China

    Guangyong Chen

  8. Department of Pathology, Institute of Basic Medical Sciences Chinese Academy of Medical Science, School of Basic Medicine Peking Union Medical College, Beijing, China

    Yamei Niu & Weimin Tong

Authors
  1. Yanmeng Li
    View author publications

    Search author on:PubMed Google Scholar

  2. Qin Ouyang
    View author publications

    Search author on:PubMed Google Scholar

  3. Zhibin Chen
    View author publications

    Search author on:PubMed Google Scholar

  4. Donghu Zhou
    View author publications

    Search author on:PubMed Google Scholar

  5. Zhenkun Li
    View author publications

    Search author on:PubMed Google Scholar

  6. Xiaoxi Yang
    View author publications

    Search author on:PubMed Google Scholar

  7. Jiang Long
    View author publications

    Search author on:PubMed Google Scholar

  8. Guangyong Chen
    View author publications

    Search author on:PubMed Google Scholar

  9. Xiaojin Li
    View author publications

    Search author on:PubMed Google Scholar

  10. Siyu Jia
    View author publications

    Search author on:PubMed Google Scholar

  11. Huaduan Zi
    View author publications

    Search author on:PubMed Google Scholar

  12. Saiping Qi
    View author publications

    Search author on:PubMed Google Scholar

  13. Hengcheng Tang
    View author publications

    Search author on:PubMed Google Scholar

  14. Bei Zhang
    View author publications

    Search author on:PubMed Google Scholar

  15. Yamei Niu
    View author publications

    Search author on:PubMed Google Scholar

  16. Anjian Xu
    View author publications

    Search author on:PubMed Google Scholar

  17. Weimin Tong
    View author publications

    Search author on:PubMed Google Scholar

  18. Jidong Jia
    View author publications

    Search author on:PubMed Google Scholar

  19. Jian Huang
    View author publications

    Search author on:PubMed Google Scholar

Contributions

JH, JDJ, WMT and AJX conceptualized and/or supervised the study; YML, QOY and ZBC performed the most experiments; AJX and DHZ provided technique supports. ZKL and XJL were engaged in animal investigations. JL and GYC acquired and managed patients. SYJ and HDZ were responsible for genetic instability detection. SPQ and HCT participated in consumable reagent support. XXY, YMN and BZ provided clinical analysis and professional assessment. YML and JH wrote the manuscript. JDJ, AJX and WMT revised the manuscript. All authors have read and approved the final manuscript.

Corresponding authors

Correspondence to Anjian Xu, Weimin Tong, Jidong Jia or Jian Huang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval and content to participate

Written informed consent was obtained from all participants according to the guidelines of the Declaration of Helsinki. The study protocols were performed in accordance with the relevant guidelines and regulations, and approved by the Clinical Research Ethics Committee of Beijing Friendship Hospital, Capital Medical University (Number 2015-P2-019-01), and Beijing You-an Hospital, Capital Medical University (Number ChiCTR-ONRC-10001064), and the Animal Experiments and Experimental Animal Welfare Committee of Beijing Friendship Hospital, Capital Medical University (Number 20-2034).

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, Y., Ouyang, Q., Chen, Z. et al. Novel role of general transcript factor IIH subunit 2 (GTF2H2) in the development and sex disparity of hepatocellular carcinoma. Oncogene 44, 1323–1335 (2025). https://doi.org/10.1038/s41388-025-03301-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41388-025-03301-7

Search

Advanced search

Quick links