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Novel STAT3 oligonucleotide compounds suppress tumor growth and overcome the acquired resistance to sorafenib in hepatocellular carcinoma

Acta Pharmacologica Sinica (2024)Cite this article

Abstract

Signal transducer and activator of transcription 3 (STAT3) plays an important role in the occurrence and progression of tumors, leading to resistance and poor prognosis. Activation of STAT3 signaling is frequently detected in hepatocellular carcinoma (HCC), but potent and less toxic STAT3 inhibitors have not been discovered. Here, based on antisense technology, we designed a series of stabilized modified antisense oligonucleotides targeting STAT3 mRNA (STAT3 ASOs). Treatment with STAT3 ASOs decreased the STAT3 mRNA and protein levels in HCC cells. STAT3 ASOs significantly inhibited the proliferation, survival, migration, and invasion of cancer cells by specifically perturbing STAT3 signaling. Treatment with STAT3 ASOs decreased the tumor burden in an HCC xenograft model. Moreover, aberrant STAT3 signaling activation is one of multiple signaling pathways involved in sorafenib resistance in HCC. STAT3 ASOs effectively sensitized resistant HCC cell lines to sorafenib in vitro and improved the inhibitory potency of sorafenib in a resistant HCC xenograft model. The developed STAT3 ASOs enrich the tools capable of targeting STAT3 and modulating STAT3 activity, serve as a promising strategy for treating HCC and other STAT3-addicted tumors, and alleviate the acquired resistance to sorafenib in HCC patients.

A series of novel STAT3 antisense oligonucleotide were designed and showed potent anti-cancer efficacy in hepatocellular carcinoma in vitro and in vivo by targeting STAT3 signaling. Moreover, the selected STAT3 ASOs enhance sorafenib sensitivity in resistant cell model and xenograft model.

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Fig. 1: Design and screening of STAT3 antisense oligonucleotides (STAT3-ASOs).
Fig. 2: STAT3 ASOs inhibited cell proliferation, survival, migration, and invasion in HCC.
Fig. 3: STAT3 ASOs selectively inhibited STAT3 signaling in HCC.
Fig. 4: STAT3 ASOs repress tumor growth of hepatoma xenograft in vivo.
Fig. 5: STAT3 ASO-2 enhanced sensitivity of sorafenib in resistant HCC cell lines.
Fig. 6: STAT3 ASO2 enhanced the anti-tumor efficacy of sorafenib in drug-resistant xenografts of HCC.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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. Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018;391:1301–14.

    Article  PubMed  Google Scholar 

  3. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90.

    Article  CAS  PubMed  Google Scholar 

  4. Zhu YJ, Zheng B, Wang HY, Chen L. New knowledge of the mechanisms of sorafenib resistance in liver cancer. Acta Pharmacol Sin. 2017;38:614–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Shi Y, Zhang Z, Qu X, Zhu X, Zhao L, Wei R, et al. Roles of STAT3 in leukemia (Review). Int J Oncol. 2018;53:7–20.

    CAS  PubMed  Google Scholar 

  6. Sriuranpong V, Park JI, Amornphimoltham P, Patel V, Nelkin BD, Gutkind JS. Epidermal growth factor receptor-independent constitutive activation of STAT3 in head and neck squamous cell carcinoma is mediated by the autocrine/paracrine stimulation of the interleukin 6/gp130 cytokine system. Cancer Res. 2003;63:2948–56.

    CAS  PubMed  Google Scholar 

  7. Banerjee K, Resat H. Constitutive activation of STAT3 in breast cancer cells: a review. Int J Cancer. 2016;138:2570–8.

    Article  CAS  PubMed  Google Scholar 

  8. Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C, et al. Stat3 as an oncogene. Cell. 1999;98:295–303.

    Article  CAS  PubMed  Google Scholar 

  9. Rawlings JS, Rosler KM, Harrison DA. The JAK/STAT signaling pathway. J Cell Sci. 2004;117:1281–3.

    Article  CAS  PubMed  Google Scholar 

  10. Logotheti S, Pützer BM. STAT3 and STAT5 targeting for simultaneous management of melanoma and autoimmune diseases. Cancers. 2019;11:1448.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Liu Y, Fuchs J, Li C, Lin J. IL-6, a risk factor for hepatocellular carcinoma: FLLL32 inhibits IL-6-induced STAT3 phosphorylation in human hepatocellular cancer cells. Cell Cycle. 2010;9:3423–7.

    Article  CAS  PubMed  Google Scholar 

  12. He G, Karin M. NF-κB and STAT3 - key players in liver inflammation and cancer. Cell Res. 2011;21:159–68.

    Article  CAS  PubMed  Google Scholar 

  13. He G, Yu GY, Temkin V, Ogata H, Kuntzen C, Sakurai T, et al. Hepatocyte IKKbeta/NF-kappaB inhibits tumor promotion and progression by preventing oxidative stress-driven STAT3 activation. Cancer Cell. 2010;17:286–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Calvisi DF, Ladu S, Gorden A, Farina M, Conner EA, Lee JS, et al. Ubiquitous activation of Ras and Jak/Stat pathways in human HCC. Gastroenterology. 2006;130:1117–28.

    Article  CAS  PubMed  Google Scholar 

  15. Lai SC, Su YT, Chi CC, Kuo YC, Lee KF, Wu YC, et al. DNMT3b/OCT4 expression confers sorafenib resistance and poor prognosis of hepatocellular carcinoma through IL-6/STAT3 regulation. J Exp Clin Cancer Res. 2019;38:474.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Chen J, Jin R, Zhao J, Liu J, Ying H, Yan H, et al. Potential molecular, cellular, and microenvironmental mechanism of sorafenib resistance in hepatocellular carcinoma. Cancer Lett. 2015;367:1–11.

    Article  CAS  PubMed  Google Scholar 

  17. Pandit SK, Sandrini G, Merulla J, Nobili V, Wang X, Zangari A, et al. Mitochondrial plasticity promotes resistance to sorafenib and vulnerability to STAT3 inhibition in human hepatocellular carcinoma. Cancers. 2021;13:6029.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ito Y, Takeda T, Sakon M, Tsujimoto M, Higashiyama S, Noda K, et al. Expression and clinical significance of erb-B receptor family in hepatocellular carcinoma. Br J Cancer. 2001;84:1377–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wang X, Hu R, Song Z, Zhao H, Pan Z, Feng Y, et al. Sorafenib combined with STAT3 knockdown triggers ER stress-induced HCC apoptosis and cGAS-STING-mediated anti-tumor immunity. Cancer Lett. 2022;547:215880.

    Article  CAS  PubMed  Google Scholar 

  20. Jiang Y, Chen P, Hu K, Dai G, Li J, Zheng D, et al. Inflammatory microenvironment of fibrotic liver promotes hepatocellular carcinoma growth, metastasis and sorafenib resistance through STAT3 activation. J Cell Mol Med. 2021;25:1568–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Shiah JV, Grandis JR, Johnson DE. Targeting STAT3 with proteolysis targeting chimeras and next-generation antisense oligonucleotides. Mol Cancer Ther. 2021;20:219–28.

    Article  CAS  PubMed  Google Scholar 

  22. Yang X, Xu L, Yang L, Xu S. Research progress of STAT3-based dual inhibitors for cancer therapy. Bioorg Med Chem. 2023;91:117382.

    Article  CAS  PubMed  Google Scholar 

  23. Baker BF, Lot SS, Kringel J, Cheng-Flournoy S, Villiet P, Sasmor HM, et al. Oligonucleotide-europium complex conjugate designed to cleave the 5’ cap structure of the ICAM-1 transcript potentiates antisense activity in cells. Nucleic Acids Res. 1999;27:1547–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Vickers TA, Wyatt JR, Burckin T, Bennett CF, Freier SM. Fully modified 2’ MOE oligonucleotides redirect polyadenylation. Nucleic Acids Res. 2001;29:1293–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ward AJ, Norrbom M, Chun S, Bennett CF, Rigo F. Nonsense-mediated decay as a terminating mechanism for antisense oligonucleotides. Nucleic Acids Res. 2014;42:5871–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Liang X-H, Nichols JG, Hsu C-W, Vickers TA, Crooke ST. mRNA levels can be reduced by antisense oligonucleotides via no-go decay pathway. Nucleic Acids Res. 2019;47:6900–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Melton DA. Injected anti-sense RNAs specifically block messenger RNA translation in vivo. Proc Natl Acad Sci USA. 1985;82:144–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Prakash TP, Kawasaki AM, Wancewicz EV, Shen L, Monia BP, Ross BS, et al. Comparing in vitro and in vivo activity of 2’-O-[2-(methylamino)-2-oxoethyl]- and 2’-O-methoxyethyl-modified antisense oligonucleotides. J Med Chem. 2008;51:2766–76.

    Article  CAS  PubMed  Google Scholar 

  29. Khvorova A, Watts JK. The chemical evolution of oligonucleotide therapies of clinical utility. Nat Biotechnol. 2017;35:238–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Quemener AM, Bachelot L, Forestier A, Donnou-Fournet E, Gilot D, Galibert M-D. The powerful world of antisense oligonucleotides: from bench to bedside. Wiley Interdiscip Rev RNA. 2020;11:e1594.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Zhu BR, Cai JM, Tang GS, Li BL, Gao F, Cui JG, et al. [Effects of STAT3 antisense oligonucleotide on proliferation and apoptosis of non-small cell lung cancer cell line A549]. Ai Zheng. 2007;26:820–7.

    CAS  PubMed  Google Scholar 

  32. Yang L, Ma X, Xiao L, Tang M, Weng X, Sun L, et al. Uniquely modified RNA oligonucleotides targeting STAT3 suppress melanoma growth both in vitro and in vivo. Cancer Biol Ther. 2009;8:2065–72.

    Article  CAS  PubMed  Google Scholar 

  33. Oweida AJ, Darragh L, Phan A, Binder D, Bhatia S, Mueller A, et al. STAT3 Modulation of regulatory T cells in response to radiation therapy in head and neck cancer. J Natl Cancer Inst. 2019;111:1339–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Gritsko T, Williams A, Turkson J, Kaneko S, Bowman T, Huang M, et al. Persistent activation of stat3 signaling induces survivin gene expression and confers resistance to apoptosis in human breast cancer cells. Clin Cancer Res. 2006;12:11–9.

    Article  CAS  PubMed  Google Scholar 

  35. Lü H, Zhang Q, Yan B. [Mitochondrial mechanisms of antisense oligodeoxynucleotide Stat3 induced apoptosis in laryngeal carcinoma cell]. Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2012;26:316–8.

    PubMed  Google Scholar 

  36. Li WC, Ye SL, Sun RX, Liu YK, Tang ZY, Kim Y, et al. Inhibition of growth and metastasis of human hepatocellular carcinoma by antisense oligonucleotide targeting signal transducer and activator of transcription 3. Clin Cancer Res. 2006;12:7140–8.

    Article  CAS  PubMed  Google Scholar 

  37. Mora LB, Buettner R, Seigne J, Diaz J, Ahmad N, Garcia R, et al. Constitutive activation of Stat3 in human prostate tumors and cell lines: direct inhibition of Stat3 signaling induces apoptosis of prostate cancer cells. Cancer Res. 2002;62:6659–66.

    CAS  PubMed  Google Scholar 

  38. Ribrag V, Lee ST, Rizzieri D, Dyer MJS, Fayad L, Kurzrock R, et al. A phase 1b study to evaluate the safety and efficacy of durvalumab in combination with tremelimumab or danvatirsen in patients with relapsed or refractory diffuse large B-cell lymphoma. Clin Lymphoma Myeloma Leuk. 2021;21:309–17.e3

    Article  CAS  PubMed  Google Scholar 

  39. Cohen EEW, Harrington KJ, Hong DS, Mesia R, Brana I, Perez Segura P, et al. A phase 1b/2 study (SCORES) of durvalumab (D) plus danvatirsen (DAN; AZD9150) or AZD5069 (CX2i) in advanced solid malignancies and recurrent/metastatic head and neck squamous cell carcinoma (RM-HNSCC): Updated results. Ann Oncol. 2018;29:372–99.

    Article  Google Scholar 

  40. Ma WK, Voss DM, Scharner J, Costa ASH, Lin KT, Jeon HY, et al. ASO-based PKM splice-switching therapy inhibits hepatocellular carcinoma growth. Cancer Res. 2022;82:900–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Xu J, Lin H, Wu G, Zhu M, Li M. IL-6/STAT3 is a promising therapeutic target for hepatocellular carcinoma. Front Oncol. 2021;11:760971.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Li Y, Rogoff HA, Keates S, Gao Y, Murikipudi S, Mikule K, et al. Suppression of cancer relapse and metastasis by inhibiting cancer stemness. Proc Natl Acad Sci USA. 2015;112:1839–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Batistatou N, Kritzer JA. Investigation of sequence-penetration relationships of antisense oligonucleotides. Chembiochem. 2023;24:e202300009.

    Article  CAS  PubMed  Google Scholar 

  44. Shao YY, Lin H, Li YS, Lee YH, Chen HM, Cheng AL, et al. High plasma interleukin-6 levels associated with poor prognosis of patients with advanced hepatocellular carcinoma. Jpn J Clin Oncol. 2017;47:949–53.

    Article  PubMed  Google Scholar 

  45. Sakurai T, Yada N, Hagiwara S, Arizumi T, Minaga K, Kamata K, et al. Gankyrin induces STAT3 activation in tumor microenvironment and sorafenib resistance in hepatocellular carcinoma. Cancer Sci. 2017;108:1996–2003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Chen RY, Yen CJ, Liu YW, Guo CG, Weng CY, Lai CH, et al. CPAP promotes angiogenesis and metastasis by enhancing STAT3 activity. Cell Death Differ. 2020;27:1259–73.

    Article  CAS  PubMed  Google Scholar 

  47. Xie L, Zeng Y, Dai Z, He W, Ke H, Lin Q, et al. Chemical and genetic inhibition of STAT3 sensitizes hepatocellular carcinoma cells to sorafenib induced cell death. Int J Biol Sci. 2018;14:577–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Zou S, Tong Q, Liu B, Huang W, Tian Y, Fu X. Targeting STAT3 in cancer immunotherapy. Mol Cancer. 2020;19:145.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Gotthardt D, Putz EM, Straka E, Kudweis P, Biaggio M, Poli V, et al. Loss of STAT3 in murine NK cells enhances NK cell-dependent tumor surveillance. Blood. 2014;124:2370–9.

    Article  CAS  PubMed  Google Scholar 

  50. Takenaka MC, Gabriely G, Rothhammer V, Mascanfroni ID, Wheeler MA, Chao C-C, et al. Control of tumor-associated macrophages and T cells in glioblastoma via AHR and CD39. Nat Neurosci. 2019;22:729–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Kortylewski M, Kujawski M, Wang T, Wei S, Zhang S, Pilon-Thomas S, et al. Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent antitumor immunity. Nat Med. 2005;11:1314–21.

    Article  CAS  PubMed  Google Scholar 

  52. Keremu A, Aimaiti A, Liang Z, Zou X. Role of the HDAC6/STAT3 pathway in regulating PD-L1 expression in osteosarcoma cell lines. Cancer Chemother Pharmacol. 2019;83:255–64.

    Article  CAS  PubMed  Google Scholar 

  53. Kitamura H, Ohno Y, Toyoshima Y, Ohtake J, Homma S, Kawamura H, et al. Interleukin-6/STAT3 signaling as a promising target to improve the efficacy of cancer immunotherapy. Cancer Sci. 2017;108:1947–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Herrmann A, Lahtz C, Nagao T, Song JY, Chan WC, Lee H, et al. CTLA4 promotes Tyk2-STAT3-dependent B-cell oncogenicity. Cancer Res. 2017;77:5118–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Moreira D, Adamus T, Zhao X, Su YL, Zhang Z, White SV, et al. STAT3 inhibition combined with CpG immunostimulation activates antitumor immunity to eradicate genetically distinct castration-resistant prostate cancers. Clin Cancer Res. 2018;24:5948–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Piper M, Van Court B, Mueller A, Watanabe S, Bickett T, Bhatia S, et al. Targeting Treg-expressed STAT3 enhances NK-mediated surveillance of metastasis and improves therapeutic response in pancreatic adenocarcinoma. Clin Cancer Res. 2022;28:1013–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Moreira D, Sampath S, Won H, White SV, Su YL, Alcantara M, et al. Myeloid cell-targeted STAT3 inhibition sensitizes head and neck cancers to radiotherapy and T cell-mediated immunity. J Clin Invest. 2021;131:e137001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Proia TA, Singh M, Woessner R, Carnevalli L, Bommakanti G, Magiera L, et al. STAT3 antisense oligonucleotide remodels the suppressive tumor microenvironment to enhance immune activation in combination with anti-PD-L1. Clin Cancer Res. 2020;26:6335–49.

    Article  CAS  PubMed  Google Scholar 

  59. Man S, Yao J, Lv P, Liu Y, Yang L, Ma L. Curcumin-enhanced antitumor effects of sorafenib via regulating the metabolism and tumor microenvironment. Food Funct. 2020;11:6422–32.

    Article  CAS  PubMed  Google Scholar 

  60. Geary RS, Norris D, Yu R, Bennett CF. Pharmacokinetics, biodistribution and cell uptake of antisense oligonucleotides. Adv Drug Deliv Rev. 2015;87:46–51.

    Article  CAS  PubMed  Google Scholar 

  61. Bennett CF. Therapeutic antisense oligonucleotides are coming of age. Annu Rev Med. 2019;70:307–21.

    Article  CAS  PubMed  Google Scholar 

  62. Crooke ST, Baker BF, Crooke RM, Liang XH. Antisense technology: an overview and prospectus. Nat Rev Drug Discov. 2021;20:427–53.

    Article  CAS  PubMed  Google Scholar 

  63. Burslem GM, Crews CM. Proteolysis-targeting chimeras as therapeutics and tools for biological discovery. Cell. 2020;181:102–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Kulkarni JA, Witzigmann D, Thomson SB, Chen S, Leavitt BR, Cullis PR, et al. The current landscape of nucleic acid therapeutics. Nat Nanotechnol. 2021;16:630–43.

    Article  CAS  PubMed  Google Scholar 

  65. Roberts TC, Langer R, Wood MJA. Advances in oligonucleotide drug delivery. Nat Rev Drug Discov. 2020;19:673–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Gupta R, Salave S, Rana D, Karunakaran B, Butreddy A, Benival D, et al. Versatility of liposomes for antisense oligonucleotide delivery: a special focus on various therapeutic areas. Pharmaceutics. 2023;15:1435.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (22077144, 81973359), Guangdong Basic and Applied Basic Research Foundation (2022A1515012204), Joint Foundation of Guangdong and Macau for Science and Technology Innovation (2022A0505020024), the Science and Technology Development Fund, Macau SAR (File No. 0053-2021-AGJ). The Key Research and Development Plan of Guangzhou City (202206080007) and Guangdong Provincial Key Laboratory of Construction Foundation (2023B1212060022) are also appreciated.

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  1. These authors contributed equally: Qi-yi Zhang, Wen Ding.

Authors and Affiliations

  1. National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation, Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China

    Qi-yi Zhang, Wen Ding, Jian-shan Mo, Shu-min Ou-yang, Zi-you Lin, Ke-ren Peng, Jin-ping Lei & Xiao-lei Zhang

  2. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China

    Guo-pin Liu & Yan-dong Wang

  3. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China

    Jin-jian Lu

  4. Department of Medicine, Division of Hematology-Oncology, and Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA

    Pei-bin Yue

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Contributions

QYZ and WD: Conception, formal analysis, investigation, write original draft. JSM: Resources, investigation, methodology. SMOY, ZYL, KRP, and GPL: Data curation, investigation, methodology. PBY, JJL, and JPL: Methodology, writing–review and editing. XLZ, and YDW: Conceptualization, design, supervision, funding acquisition, writing–review and editing.

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Correspondence to Yan-dong Wang or Xiao-lei Zhang.

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Zhang, Qy., Ding, W., Mo, Js. et al. Novel STAT3 oligonucleotide compounds suppress tumor growth and overcome the acquired resistance to sorafenib in hepatocellular carcinoma. Acta Pharmacol Sin (2024). https://doi.org/10.1038/s41401-024-01261-4

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