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:

HN1-mediated activation of lipogenesis through Akt-SREBP signaling promotes hepatocellular carcinoma cell proliferation and metastasis

Cancer Gene Therapy (2024)Cite this article

Subjects

Abstract

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide, with more than 800,000 deaths each year, and its 5-year survival rate is less than 12%. The role of the HN1 gene in HCC has remained elusive, despite its upregulation in various cancer types. In our investigation, we identified HN1’s heightened expression in HCC tissues, which, upon overexpression, fosters cell proliferation, migration, and invasion, unveiling its role as an oncogene in HCC. In addition, silencing HN1 diminished the viability and metastasis of HCC cells, whereas HN1 overexpression stimulated their growth and invasion. Gene expression profiling revealed HN1 silencing downregulated 379 genes and upregulated 130 genes, and suppressive proteins associated with the lipogenic signaling pathway networks. Notably, suppressing HN1 markedly decreased the expression levels of SREBP1 and SREBP2, whereas elevating HN1 had the converse effect. This dual modulation of HN1 affected lipid formation, hindering it upon HN1 silencing and promoting it upon HN1 overexpression. Moreover, HN1 triggers the Akt pathway, fostering tumorigenesis via SREBP1-mediated lipogenesis and silencing HN1 effectively curbed HCC tumor growth in mouse xenograft models by deactivating SREBP-1, emphasizing the potential of HN1 as a therapeutic target, impacting both external and internal factors, it holds promise as an effective therapeutic strategy for HCC.

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

Access options

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: HN1 is overexpressed in human HCC and correlates with poor prognosis and promoter methylation.
Fig. 2: Effects of HN1 on cell proliferation and apoptosis in HCC.
Fig. 3: Effects of HN1 on the cell cycle in HCC.
Fig. 4: Effects of HN1 on cell migration and invasion in HCC.
Fig. 5: Gene expression levels affected by HN1 knockdown in HCC.
Fig. 6: HN1 regulated by Akt in HCC.
Fig. 7: HN1 regulated SREBP-1 and SREBP-2 in HCC.
Fig. 8: HN1 regulated lipogenesis in HCC.
Fig. 9: HN1 regulated proliferation and lipogenesis through SREBP-1 in HCC.
Fig. 10: Knockdown of HN1 inhibited tumorigenesis in xenograft mice.
Fig. 11: Inhibition of SREBP reverses the tumorigenic effect of HN1 in xenograft mice.
Fig. 12: Schematic representation of HN1-mediated inhibition of tumorigenesis of HCC.

Similar content being viewed by others

Data availability

All the data generated or analyzed during this study are included in this published article.

References

  1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49.

    Article  PubMed  Google Scholar 

  2. Cao W, Chen HD, Yu YW, Li N, Chen WQ. Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020. Chin Med J. 2021;134:783–91.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Liu Y, Zheng J, Hao J, Wang RR, Liu X, Gu P, et al. Global burden of primary liver cancer by five etiologies and global prediction by 2035 based on global burden of disease study 2019. Cancer Med. 2022;11:1310–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Chidambaranathan-Reghupaty S, Fisher PB, Sarkar D. Hepatocellular carcinoma (HCC): epidemiology, etiology and molecular classification. Adv Cancer Res. 2021;149:1–61.

    Article  CAS  PubMed  Google Scholar 

  5. Farah M, Anugwom C, Ferrer JD, Baca EL, Mattos AZ, Possebon JPP, et al. Changing epidemiology of hepatocellular carcinoma in South America: a report from the South American liver research network. Ann Hepatol. 2023;28:100876.

    Article  PubMed  Google Scholar 

  6. Tran NH. Shifting epidemiology of hepatocellular carcinoma in far eastern and southeast Asian patients: explanations and implications. Curr Oncol Rep. 2022;24:187–93.

    Article  PubMed  Google Scholar 

  7. Lliovet, J. M. et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2021;7:6.

  8. Konyn P, Ahmed A, Kim D. Current epidemiology in hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol. 2021;15:1295–307.

    Article  CAS  PubMed  Google Scholar 

  9. Mehta N, Bhangui P, Yao FY, Mazzaferro V, Toso C, Akamatsu N, et al. Liver transplantation for hepatocellular carcinoma. working group report from the ILTS transplant oncology consensus conference. Transplantation. 2020;104:1136–42.

    Article  PubMed  Google Scholar 

  10. Berenguer M, Burra P, Ghobrial M, Hibi T, Metselaar H, Sapisochin G, et al. Posttransplant management of recipients undergoing liver transplantation for hepatocellular carcinoma. Working group report from the ILTS transplant oncology consensus conference. Transplantation. 2020;104:1143–9.

    Article  PubMed  Google Scholar 

  11. Bednarsch J, Czigany Z, Heise D, Joechle K, Luedde T, Heij L, et al. Prognostic evaluation of HCC patients undergoing surgical resection: an analysis of 8 different staging systems. Langenbecks Arch Surg. 2021;406:75–86.

    Article  PubMed  Google Scholar 

  12. Zhang W, Zhang B, Chen XP. Adjuvant treatment strategy after curative resection for hepatocellular carcinoma. Front Med. 2021;15:155–69.

    Article  PubMed  Google Scholar 

  13. Tellapuri S, Sutphin PD, Beg MS, Singal AG, Kalva SP. Staging systems of hepatocellular carcinoma: a review. Ind J Gastroenterol. 2018;37:481–91.

    Article  Google Scholar 

  14. Tumen D, Heumann P, Gulow K, Demirci CN, Cosma LS, Muller M, et al. Pathogenesis and current treatment strategies of hepatocellular carcinoma. Biomedicines. 2022;10:3202.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Bruix J, Reig M, Sherman M. Evidence-based diagnosis, staging, and treatment of patients with hepatocellular carcinoma. Gastroenterology. 2016;150:835–53.

    Article  PubMed  Google Scholar 

  16. Ahn JC, Teng PC, Chen PJ, Posadas E, Tseng HR, Lu SC, et al. Detection of circulating tumor cells and their implications as a biomarker for diagnosis, prognostication, and therapeutic monitoring in hepatocellular carcinoma. Hepatology. 2021;73:422–36.

    Article  PubMed  Google Scholar 

  17. Salazar J, Le A. The heterogeneity of liver cancer metabolism. Adv Exp Med Biol. 2021;1311:127–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Laughlin KM, Luo D, Liu C, Shaw G, Warrington KH Jr, Law BK, et al. Hematopoietic- and neurologic-expressed sequence 1 (Hn1) depletion in B16.F10 melanoma cells promotes a differentiated phenotype that includes increased melanogenesis and cell cycle arrest. Differentiation. 2009;78:35–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Varisli L. Decreased expression of HN1 sensitizes prostate cancer cells to apoptosis induced by docetaxel and 2-methoxyestradiol. Ann Clin Lab Sci. 2022;52:196–201.

    CAS  PubMed  Google Scholar 

  20. Zhang C, Xu B, Lu S, Zhao Y, Liu P. HN1 contributes to migration, invasion, and tumorigenesis of breast cancer by enhancing MYC activity. Mol Cancer. 2017;16:90.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Pan Z, Fang Q, Li L, Zhang Y, Xu T, Liu Y, et al. HN1 promotes tumor growth and metastasis of anaplastic thyroid carcinoma by interacting with STMN1. Cancer Lett. 2021;501:31–42.

    Article  CAS  PubMed  Google Scholar 

  22. Wang R, Fu Y, Yao M, Cui X, Zhao Y, Lu X, et al. The HN1/HMGB1 axis promotes the proliferation and metastasis of hepatocellular carcinoma and attenuates the chemosensitivity to oxaliplatin. FEBS J. 2022;289:6400–19.

    Article  CAS  PubMed  Google Scholar 

  23. Chen J, Qiu J, Li F, Jiang X, Sun X, Zheng L, et al. HN1 promotes tumor associated lymphangiogenesis and lymph node metastasis via NF-kappaB signaling activation in cervical carcinoma. Biochem Biophys Res Commun. 2020;530:87–94.

    Article  CAS  PubMed  Google Scholar 

  24. Goto T, Tokunaga F, Hisatomi O. Hematological- and neurological-expressed sequence 1 gene products in progenitor cells during newt retinal development. Stem Cells Int. 2012;2012:436042.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Lee JS, Chu IS, Heo J, Calvisi DF, Sun Z, Roskams T, et al. Classification and prediction of survival in hepatocellular carcinoma by gene expression profiling. Hepatology. 2004;40:667–76.

    Article  CAS  PubMed  Google Scholar 

  26. Lee JS, Thorgeirsson SS. Genome-scale profiling of gene expression in hepatocellular carcinoma: classification, survival prediction, and identification of therapeutic targets. Gastroenterology. 2004;127:S51–55.

    Article  CAS  PubMed  Google Scholar 

  27. Woo HG, Park ES, Cheon JH, Kim JH, Lee JS, Park BJ, et al. Gene expression-based recurrence prediction of hepatitis B virus-related human hepatocellular carcinoma. Clin Cancer Res. 2008;14:2056–64.

    Article  CAS  PubMed  Google Scholar 

  28. Kim SM, Leem SH, Chu IS, Park YY, Kim SC, Kim SB, et al. Sixty-five gene-based risk score classifier predicts overall survival in hepatocellular carcinoma. Hepatology. 2012;55:1443–52.

    Article  PubMed  Google Scholar 

  29. Nault JC, De Reynies A, Villanueva A, Calderaro J, Rebouissou S, Couchy G, et al. A hepatocellular carcinoma 5-gene score associated with survival of patients after liver resection. Gastroenterology. 2013;145:176–87.

    Article  CAS  PubMed  Google Scholar 

  30. Ricoult SJ, Yecies JL, Ben-Sahra I, Manning BD. Oncogenic PI3K and K-Ras stimulate de novo lipid synthesis through mTORC1 and SREBP. Oncogene. 2016;35:1250–60.

    Article  CAS  PubMed  Google Scholar 

  31. Yecies JL, Zhang HH, Menon S, Liu S, Yecies D, Lipovsky AI, et al. Akt stimulates hepatic SREBP1c and lipogenesis through parallel mTORC1-dependent and independent pathways. Cell Metab. 2011;14:21–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Zhao Q, Lin X, Wang G. Targeting SREBP-1-mediated lipogenesis as potential strategies for cancer. Front Oncol. 2022;12:952371.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Du X, Pham YH, Brown AJ. Effects of 25-hydroxycholesterol on cholesterol esterification and sterol regulatory element-binding protein processing are dissociable: implications for cholesterol movement to the regulatory pool in the endoplasmic reticulum. J Biol Chem. 2004;279:47010–6.

    Article  CAS  PubMed  Google Scholar 

  34. Ferre P, Phan F, Foufelle F. SREBP-1c and lipogenesis in the liver: an update1. Biochem J. 2021;478:3723–39.

    Article  CAS  PubMed  Google Scholar 

  35. Wu X, Romero D, Swiatek WI, Dorweiler I, Kikani CK, Sabic H, et al. PAS kinase drives lipogenesis through SREBP-1 maturation. Cell Rep. 2014;8:242–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Cheng C, Ru P, Geng F, Liu J, Yoo JY, Wu X, et al. Glucose-mediated N-glycosylation of SCAP is essential for SREBP-1 activation and tumor growth. Cancer Cell. 2015;28:569–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Cheng C, Geng F, Li Z, Zhong Y, Wang H, Cheng X, et al. Ammonia stimulates SCAP/Insig dissociation and SREBP-1 activation to promote lipogenesis and tumour growth. Nat. Metab. 2022;4:575–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Zane KE, Nagib PB, Jalil S, Mumtaz K, Makary MS. Emerging curative-intent minimally-invasive therapies for hepatocellular carcinoma. World J Hepatol. 2022;14:885–95.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Chang KV, Chen JD, Wu WT, Huang KC, Hsu CT, Han DS. Association between loss of skeletal muscle mass and mortality and tumor recurrence in hepatocellular carcinoma: a systematic review and meta-analysis. Liver Cancer. 2018;7:90–103.

    Article  PubMed  Google Scholar 

  40. Chen S, Ji R, Shi X, Wang Z, Zhu D. Retrospective analysis of efficacy, safety, and prognostic factors in a cohort of Chinese hepatocellular carcinoma patients treated with drug-eluting bead transarterial chemoembolization. Braz J Med Biol Res. 2019;52:e8467.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Sparchez Z, Mocan T, Radu P, Mocan LP, Sparchez M, Leucuta DC, et al. Prognostic factors after percutaneous radiofrequency ablation in the treatment of hepatocellular carcinoma. Impact of incomplete ablation on recurrence and overall survival rates. J Gastrointestin Liver Dis. 2018;27:399–407.

    Article  PubMed  Google Scholar 

  42. Hart MJ, de los Santos R, Albert IN, Rubinfeld B, Polakis P. Downregulation of beta-catenin by human Axin and its association with the APC tumor suppressor, beta-catenin and GSK3 beta. Curr Biol. 1998;8:573–81.

    Article  CAS  PubMed  Google Scholar 

  43. Varisli L, Ozturk BE, Akyuz GK, Korkmaz KS. HN1 negatively influences the beta-catenin/E-cadherin interaction, and contributes to migration in prostate cells. J Cell Biochem. 2015;116:170–8.

    Article  CAS  PubMed  Google Scholar 

  44. Park JH, Pyun WY, Park HW. Cancer metabolism: phenotype, signaling and therapeutic targets. Cells. 2020;9:2308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Koundouros N, Poulogiannis G. Reprogramming of fatty acid metabolism in cancer. Br J Cancer. 2020;122:4–22.

    Article  CAS  PubMed  Google Scholar 

  46. Sun Y, Wu L, Zhong Y, Zhou K, Hou Y, Wang Z, et al. Single-cell landscape of the ecosystem in early-relapse hepatocellular carcinoma. Cell. 2021;184:404–421.e416.

    Article  CAS  PubMed  Google Scholar 

  47. Deng M, Sun S, Zhao R, Guan R, Zhang Z, Li S, et al. The pyroptosis-related gene signature predicts prognosis and indicates immune activity in hepatocellular carcinoma. Mol Med. 2022;28:16.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Shimada S, Mogushi K, Akiyama Y, Furuyama T, Watanabe S, Ogura T, et al. Comprehensive molecular and immunological characterization of hepatocellular carcinoma. EBioMedicine. 2019;40:457–70.

    Article  PubMed  Google Scholar 

  49. Fortin J, Mak TW. Targeting PI3K signaling in cancer: a cautionary tale of two AKTs. Cancer Cell. 2016;29:429–31.

    Article  CAS  PubMed  Google Scholar 

  50. Revathidevi S, Munirajan AK. Akt in cancer: mediator and more. Semin Cancer Biol. 2019;59:80–91.

    Article  CAS  PubMed  Google Scholar 

  51. Altomare DA, Khaled AR. Homeostasis and the importance for a balance between AKT/mTOR activity and intracellular signaling. Curr Med Chem. 2012;19:3748–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Yu JS, Cui W. Proliferation, survival and metabolism: the role of PI3K/AKT/mTOR signalling in pluripotency and cell fate determination. Development. 2016;143:3050–60.

    Article  CAS  PubMed  Google Scholar 

  53. He Y, Sun MM, Zhang GG, Yang J, Chen KS, Xu WW, et al. Targeting PI3K/Akt signal transduction for cancer therapy. Signal Transduct Target Ther. 2021;6:425.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Varisli L, Gonen-Korkmaz C, Debelec-Butuner B, Erbaykent-Tepedelen B, Muhammed HS, Bogurcu N, et al. Ubiquitously expressed hematological and neurological expressed 1 downregulates Akt-mediated GSK3beta signaling, and its knockdown results in deregulated G2/M transition in prostate cells. DNA Cell Biol. 2011;30:419–29.

    Article  CAS  PubMed  Google Scholar 

  55. Tian LY, Smit DJ, Jucker M. The role of PI3K/AKT/mTOR signaling in hepatocellular carcinoma metabolism. Int J Mol Sci. 2023;24:2652.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Davies BR, Greenwood H, Dudley P, Crafter C, Yu DH, Zhang J, et al. Preclinical pharmacology of AZD5363, an inhibitor of AKT: pharmacodynamics, antitumor activity, and correlation of monotherapy activity with genetic background. Mol Cancer Ther. 2012;11:873–87.

    Article  CAS  PubMed  Google Scholar 

  57. Rishi V, Gal J, Krylov D, Fridriksson J, Boysen MS, Mandrup S, et al. SREBP-1 dimerization specificity maps to both the helix-loop-helix and leucine zipper domains: use of a dominant negative. J Biol Chem. 2004;279:11863–74.

    Article  CAS  PubMed  Google Scholar 

  58. Cheng C, Geng F, Cheng X, Guo D. Lipid metabolism reprogramming and its potential targets in cancer. Cancer Commun. 2018;38:27.

    Article  Google Scholar 

  59. Zhu T, Wang Z, Zou T, Xu L, Zhang S, Chen Y, et al. SOAT1 promotes gastric cancer lymph node metastasis through lipid synthesis. Front Pharmacol. 2021;12:769647.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Chen H, Qi Q, Wu N, Wang Y, Feng Q, Jin R, et al. Aspirin promotes RSL3-induced ferroptosis by suppressing mTOR/SREBP-1/SCD1-mediated lipogenesis in PIK3CA-mutatnt colorectal cancer. Redox Biol. 2022;55:102426.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Zhao S, Cheng L, Shi Y, Li J, Yun Q, Yang H. MIEF2 reprograms lipid metabolism to drive progression of ovarian cancer through ROS/AKT/mTOR signaling pathway. Cell Death Dis. 2021;12:18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Du F, Zhang HJ, Shao W, Tu YY, Yang KJ, Piao LS. Adenosine diphosphate-ribosylation factor-like 15 can regulate glycolysis and lipogenesis related genes in colon cancer. J Physiol Pharmacol. 2022;73:403–11.

    Google Scholar 

  63. Jin Y, Chen Z, Dong J, Wang B, Fan S, Yang X, et al. SREBP1/FASN/cholesterol axis facilitates radioresistance in colorectal cancer. FEBS Open Bio. 2021;11:1343–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Zhou C, Qian W, Li J, Ma J, Chen X, Jiang Z, et al. High glucose microenvironment accelerates tumor growth via SREBP1-autophagy axis in pancreatic cancer. J Exp Clin Cancer Res. 2019;38:302.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Li C, Zhang L, Qiu Z, Deng W, Wang W. Key molecules of fatty acid metabolism in gastric cancer. Biomolecules. 2022;12:706.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Tan YT, Lin JF, Li T, Li JJ, Xu RH, Ju HQ. LncRNA-mediated posttranslational modifications and reprogramming of energy metabolism in cancer. Cancer Commun. 2021;41:109–20.

    Article  Google Scholar 

  67. Pavlova NN, Zhu J, Thompson CB. The hallmarks of cancer metabolism: still emerging. Cell Metab. 2022;34:355–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Zanotelli MR, Zhang J, Reinhart-King CA. Mechanoresponsive metabolism in cancer cell migration and metastasis. Cell Metab. 2021;33:1307–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Boroughs LK, DeBerardinis RJ. Metabolic pathways promoting cancer cell survival and growth. Nat Cell Biol. 2015;17:351–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Liu W, Chakraborty B, Safi R, Kazmin D, Chang CY, McDonnell DP. Dysregulated cholesterol homeostasis results in resistance to ferroptosis increasing tumorigenicity and metastasis in cancer. Nat Commun. 2021;12:5103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Holthuis JC, Menon AK. Lipid landscapes and pipelines in membrane homeostasis. Nature. 2014;510:48–57.

    Article  CAS  PubMed  Google Scholar 

  72. Lien EC, Westermark AM, Zhang Y, Yuan C, Li Z, Lau AN, et al. Low glycaemic diets alter lipid metabolism to influence tumour growth. Nature. 2021;599:302–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Stine ZE, Schug ZT, Salvino JM, Dang CV. Targeting cancer metabolism in the era of precision oncology. Nat Rev Drug Discov. 2022;21:141–62.

    Article  CAS  PubMed  Google Scholar 

  74. Kubik J, Humeniuk E, Adamczuk G, Madej-Czerwonka B, Korga-Plewko A. Targeting energy metabolism in cancer treatment. Int J Mol Sci. 2022;23:5572.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Zdralevic M, Vucetic M, Daher B, Marchiq I, Parks SK, Pouyssegur J. Disrupting the ‘Warburg effect’ re-routes cancer cells to OXPHOS offering a vulnerability point via ‘ferroptosis’-induced cell death. Adv Biol Regul. 2018;68:55–63.

    Article  CAS  PubMed  Google Scholar 

  76. Gwangwa MV, Joubert AM, Visagie MH. Crosstalk between the Warburg effect, redox regulation and autophagy induction in tumourigenesis. Cell Mol Biol Lett. 2018;23:20.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Jing ZL, Liu QM, He XY, Jia ZR, Xu ZZ, Yang BL, et al. NCAPD3 enhances Warburg effect through c-myc and E2F1 and promotes the occurrence and progression of colorectal cancer. J Exp Clin Canc Res. 2022;41:198.

    Article  CAS  Google Scholar 

  78. Maley CC, Galipeau PC, Finley JC, Wongsurawat VJ, Li X, Sanchez CA, et al. Genetic clonal diversity predicts progression to esophageal adenocarcinoma. Nat Genet. 2006;38:468–73.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The National Research Foundation (NRF), which is sponsored by the Korean government, provided funding for this study through the Basic Science Research Program (2021R1A2C2013505) and the Medical Research Center Program (NRF-2017R1A5A2015061) (MSIP).

Author information

Author notes

  1. These authors contributed equally: Hua Jin, Ruoyu Meng.

Authors and Affiliations

  1. Department of Physiology, Institute for Medical Sciences, Jeonbuk National University Medical School, Jeonju, 54907, Republic of Korea

    Hua Jin, Ruoyu Meng, Cong Shan Li & Soo Mi Kim

  2. School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100084, China

    Hua Jin

  3. Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, 250021, China

    Ruoyu Meng

  4. Division of Gastroenterology, Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju, 54907, Republic of Korea

    Seong-Hun Kim

  5. Department of Anatomy, Institute for Medical Sciences, Jeonbuk National University Medical School, Jeonju, 54907, Republic of Korea

    Ok Hee Chai

  6. Department of Oral Anatomy, School of Dentistry, Jeonbuk National University, Jeonju, 54907, Republic of Korea

    Young-Hoon Lee

  7. Graduate School of Medical Science and Engineering, Korean Advanced Institute of Science and Technology, Daejon, 34141, Republic of Korea

    Byung-Hyun Park

  8. Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, 77045, TX, USA

    Ju-Seog Lee

Authors
  1. Hua Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ruoyu Meng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cong Shan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Seong-Hun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ok Hee Chai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Young-Hoon Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Byung-Hyun Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ju-Seog Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Soo Mi Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HJ and RM wrote the draft and performed biological experiments. CSL conducted the experimental studies and analytical assistance from S-HK, OHC, and B-HP on the various cellular experiments. Y-HL and J-SL conducted the histology study and statistical analyses. SMK designed the experiments and described the paper. The final draft of the manuscript was reviewed and approved by all the authors.

Corresponding author

Correspondence to Soo Mi Kim.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

The human study was conducted following approval from the Ethics Committee of the University of Texas MD Anderson Cancer Center (LAB09-0687) in accordance with the Helsinki Declaration of 1975. Written informed consent was obtained from all patients prior to their inclusion in the study. All animal care procedures and sacrifices were carried out in strict accordance with protocols approved by the Institutional Animal Care and Use Committee (IACUC) and the Center for Animal Experiments at Jeonbuk National University (CBNU 2020-072).

Additional information

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

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

Jin, H., Meng, R., Li, C.S. et al. HN1-mediated activation of lipogenesis through Akt-SREBP signaling promotes hepatocellular carcinoma cell proliferation and metastasis. Cancer Gene Ther (2024). https://doi.org/10.1038/s41417-024-00827-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41417-024-00827-y

Search

Advanced search

Quick links