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Article Open Access

REV1‑targeting inhibitor JH‑RE‑06 induces ferroptosis via NCOA4‑mediated ferritinophagy in colorectal cancer cells

  • Authors:
    • Jianhua Cheng
    • Xiaoxia Yang
    • Wen Zhao
    • Jie Xu
    • Yanjie Hao
    • Fang Xu
  • View Affiliations / Copyright

    Affiliations: School of Basic Medicine, Ningxia Medical University, Yinchuan, Ningxia Hui 750001, P.R. China, Department of Anesthesia and Perioperative Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui 750004, P.R. China
    Copyright: © Cheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 159
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    Published online on: September 22, 2025
       https://doi.org/10.3892/or.2025.8992
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Abstract

Oncogenes accelerate DNA replication, leading to the activation of excessive replication origins. This process triggers replication stress (RS) and genomic instability in cancer cells, positioning RS as a promising therapeutic target. Translesion synthesis (TLS) functions as a DNA damage repair bypass mechanism, compensating for RS and conferring a proliferation advantage to cancer cells. Despite its therapeutic potential, the application of the TLS polymerase REV1 (REV1 DNA directed polymerase (REV1) inhibitor JH‑RE‑06 in colorectal cancer (CRC) remains unexplored. Bioinformatics analysis of clinical samples from The Cancer Genome Atlas (TCGA) database demonstrated marked REV1 upregulation in colorectal tumors compared with normal tissues, which was associated with a poorer prognosis. JH‑RE‑06 effectively suppressed CRC tumorigenesis both in vitro and in vivo. Mechanistically, drug rescue experiments and proteomics revealed that cell death triggered by JH‑RE‑06 was associated with elevated oxidative stress and induction of ferroptosis‑associated signaling. Transmission electron microscopy revealed characteristic morphological changes associated with ferroptosis, including a significant reduction in mitochondrial abundance and the presence of autophagic vacuoles containing engulfed mitochondria. Biochemical assays confirmed that JH‑RE‑06 significantly increased intracellular Fe²+ and malondialdehyde (MDA) levels while reducing glutathione levels, indicative of ferroptosis. Western blot analysis revealed decreased levels of antioxidant proteins, including superoxide dismutase 2 (SOD2) and glutamate‑cysteine ligase catalytic subunit (GCLC), as well as ferritin. Furthermore, western blot and FerroOrange assays, combined with Autophagy‑related Gene 7 (ATG7) and Nuclear Receptor Coactivator 4 (NCOA4) knockdown experiments, demonstrated that JH‑RE‑06 activated ferroptosis in CRC via NCOA4‑mediated ferritinophagy. Safety evaluation via hematoxylin and eosin staining of major organs in mice showed no notable pathological damage induced by JH‑RE‑06. Taken together, these findings establish REV1 as a potential diagnostic biomarker and therapeutic target in CRC. REV1 inhibitor JH‑RE‑06 promoted NCOA4‑mediated ferritinophagy and induced programmed cell death, thereby highlighting its potential as a safe and effective therapeutic strategy for CRC.
View Figures

Figure 1

REV1 expression is upregulated in CRC
tissues and associated with poor prognosis. (A) Analysis of 644
unpaired samples from TCGA database revealed elevated expression of
the REV1 and its binding partner REV7 in clinical CRC samples. (B)
Analysis of 50 paired samples from TCGA database showed that REV1
and REV7 were significantly more highly expressed in cancer
compared with adjacent non-cancerous tissue. (C) Prognostic
analysis of REV1 in CRC was performed using PrognoScan database
datasets (accession no. GSE17536/37). (D) REV1 expression levels
were analyzed in 35 paired CRC tissue samples using a tissue
microarray, which revealed significantly elevated REV1 expression
in CRC vs. adjacent normal tissue. (E) Representative
immunohistochemical REV1 staining in CRC tissue. Scale bar, 50 µm.
***P<0.001, **P<0.01, *P<0.05. REV1, REV1 DNA directed
polymerase; CRC, colorectal cancer; TCGA, The Cancer Genome Atlas;
TPM, transcripts per kilobase of exon model per million mapped
reads; DFS, disease-free survival; OS, overall survival; DSS,
disease-specific survival; OD, optical density.

Figure 2

JH, a REV1 DNA directed polymerase
inhibitor, suppresses CRC tumorigenesis both in vitro and
in vivo. (A) Cell viability assessed by Cell Counting Kit-8
revealed differential sensitivity to JH, with sustained effects
observed at 72 h vs. 24 h in CRC models. WB analysis was used to
detect γH2AX levels in cells treated with JH for 24 h. For HCT116
cells, JHL represents 1.5 and JHH represents 3.0 µM JH. For SW620
cells, JHL represents 1.0 and JHH represents 1.5 µM JH.
Concentrations were selected based on treatments that resulted in
~50% cell viability after 24 or 72 h. GAPDH was used as the
internal control. (B) Immunofluorescence staining of γH2AX in
HCT116 cells treated with 3.0 µM JH and/or 5.0 µM OXA for 12 and 24
h. Scale bar, 20 µm. (C) WB analysis of γH2AX levels after
treatment with JH and/or OXA, with GAPDH as the loading control.
Quantitative analysis revealed no significant differences between
the JH and OXA-JH treatment groups. (D) Tumor growth curves for
OXA-resistant HCT116 cell xenografts in mice. (E) Representative
immunohistochemical images of PCNA and Ki-67 staining in tumor
sections. Scale bar, 50 µm. **P<0.01, *P<0.05. CRC,
colorectal cancer; JHH, JH-RE-06 high; JHL, JH-RE-06 low; WB,
western blot; H2AX, histone H2AX; OXA, oxaliplatin; PCNA,
proliferating cell nuclear antigen; Con, control; ns, not
significant.

Figure 3

Cell death induced by REV1 DNA
directed polymerase inhibition is associated with oxidative stress
and ferroptosis. Viability of (A) HCT116 cells treated with 3 µM JH
and (B) SW620 cells treated with 1.5 µM JH in the presence or
absence of inhibitors. (C) Differentially expressed proteins
enriched by proteomics. Compared with the DMSO group, JH
upregulated 192 proteins and downregulated 458 proteins. (D)
Downregulated pathways. The top 20 enriched KEGG pathways are
illustrated. (E) Upregulated pathways. (F) Hierarchical clustering
of differentially expressed mitochondrial-associated genes.
****P<0.0001, *P<0.05. JH, JH-RE-06; KEGG, Kyoto encyclopedia
of genes and genomes; DFO, deferoxamine; Z-VAD, z-vad-fmk; Nec,
necrostatin-1; CQ, chloroquine; NAC, n-acetylcysteine; L-PEN,
l-penicillamine; ME, 2-mercaptoethanol; ns, not significant; Con,
control; FC, fold change; MRPL, mitochondrial ribosomal protein
large subunit; MRPS, mitochondrial ribosomal protein small subunit;
NDUF, NADH:ubiquinone oxidoreductase subunit.

Figure 4

JH triggers ferroptosis in colorectal
cancer cells. Transmission electron microscopy of (A) HCT116 and
(B) SW620 cells treated with JHL and JHH for 24 h show
intracellular vacuolar changes, with mitochondria-like structures
undergoing digestion inside the vacuoles. Scale bar, 5 µm. Changes
in intracellular Fe2+ concentration, MDA and GSH levels
(normalized to total protein) in (C) HCT116 cells treated with 3.0
µM JH and (D) SW620 cells treated with 1.5 µM JH at 6, 12 and 24 h
post-treatment. (E) Relative protein expression levels of SOD2, FTL
and GCLC following 12 and 24 h JH treatment in HCT116 cells; 24 h
exposure to JH resulted in significant downregulation of
antioxidant proteins SOD2, FTL and GCLC. ****P<0.0001,
***P<0.001, **P<0.01, *P<0.05. JHH, JH-RE-06 high; JHL,
JH-RE-06 low; MDA, malondialdehyde; GSH, glutathione; SOD2,
superoxide dismutase 2; FTL, ferritin light chain; GCLC,
glutamate-cysteine ligase catalytic subunit; ns, not significant;
Con, control.

Figure 5

JH triggers ferroptosis via
NCOA4-mediated ferritinophagy in colorectal cancer cells. (A)
HCT116 cells were treated with 3.0 µM JH and (B) SW620 cells with
1.5 µM JH and/or 50 µM DFO for 12 and 24 h before WB analysis for
p62, LC3, NCOA4 and FTH1, normalized to GAPDH. (C) WB analysis of
HCT116 cells with or without ATG7 knockout, treated with 3.0 µM JH.
(D) HCT116 cells were transfected with scramble or siNCOA4 for 48
h, then treated with 3.0 µM JH for 24 h. Cells were incubated with
FerroOrange probe and imaged using laser confocal microscopy. Scale
bar, 50 µm. (E) Lipid peroxidation levels were measured in ATG7 and
NCOA4 knockdown cells, as well as wild-type HCT116 and SW620 cells,
treated with JH. ***P<0.001, **P<0.01, *P<0.05. JH,
JH-RE-06; NCOA4, nuclear receptor coactivator 4; WB, western blot;
LC3, microtubule-associated protein 1 light chain 3; FTH, ferritin
heavy chain; ATG, autophagy-related gene; si, small interfering;
DFO, deferoxamine.
View References

1 

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021.PubMed/NCBI

2 

Liu Z, Xu Y, Xu G, Baklaushev VP, Chekhonin VP, Peltzer K, Ma W, Wang X, Wang G and Zhang C: Nomogram for predicting overall survival in colorectal cancer with distant metastasis. BMC Gastroenterol. 21:1032021. View Article : Google Scholar : PubMed/NCBI

3 

Veenstra CM and Krauss JC: Emerging systemic therapies for colorectal cancer. Clin Colon Rectal Surg. 31:179–191. 2018. View Article : Google Scholar : PubMed/NCBI

4 

Berti M, Cortez D and Lopes M: The plasticity of DNA replication forks in response to clinically relevant genotoxic stress. Nat Rev Mol Cell Biol. 21:633–651. 2020. View Article : Google Scholar : PubMed/NCBI

5 

Yang W and Gao Y: Translesion and repair DNA polymerases: Diverse structure and mechanism. Annu Rev Biochem. 87:239–261. 2018. View Article : Google Scholar : PubMed/NCBI

6 

Hicks JK, Chute CL, Paulsen MT, Ragland RL, Howlett NG, Gueranger Q, Glover TW and Canman CE: Differential roles for DNA polymerases eta, zeta, and REV1 in lesion bypass of intrastrand versus interstrand DNA cross-links. Mol Cell Biol. 30:1217–1230. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Sharma S, Hicks JK, Chute CL, Brennan JR, Ahn JY, Glover TW and Canman CE: REV1 and polymerase ζ facilitate homologous recombination repair. Nucleic Acids Res. 40:682–691. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Baranovskiy AG, Lada AG, Siebler HM, Zhang Y, Pavlov YI and Tahirov TH: DNA polymerase delta and zeta switch by sharing accessory subunits of DNA polymerase delta. J Biol Chem. 287:17281–17287. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Mellor C, Nassar J, Šviković S and Sale JE: PRIMPOL ensures robust handoff between on-the-fly and post-replicative DNA lesion bypass. Nucleic Acids Res. 52:243–258. 2024. View Article : Google Scholar : PubMed/NCBI

10 

Taglialatela A, Leuzzi G, Sannino V, Cuella-Martin R, Huang JW, Wu-Baer F, Baer R, Costanzo V and Ciccia A: REV1-Polzeta maintains the viability of homologous recombination-deficient cancer cells through mutagenic repair of PRIMPOL-dependent ssDNA gaps. Mol Cell. 81:4008–4025. e72021. View Article : Google Scholar : PubMed/NCBI

11 

Nayak S, Calvo JA, Cong K, Peng M, Berthiaume E, Jackson J, Zaino AM, Vindigni A, Hadden MK and Cantor SB: Inhibition of the translesion synthesis polymerase REV1 exploits replication gaps as a cancer vulnerability. Sci Adv. 6:eaaz78082020. View Article : Google Scholar : PubMed/NCBI

12 

Nayak S, Calvo JA and Cantor SB: Targeting translesion synthesis (TLS) to expose replication gaps, a unique cancer vulnerability. Expert Opin Ther Targets. 25:27–36. 2021. View Article : Google Scholar : PubMed/NCBI

13 

Lin X and Howell SB: DNA mismatch repair and p53 function are major determinants of the rate of development of cisplatin resistance. Mol Cancer Ther. 5:1239–1247. 2006. View Article : Google Scholar : PubMed/NCBI

14 

Sasatani M, Xi Y, Kajimura J, Kawamura T, Piao J, Masuda Y, Honda H, Kubo K, Mikamoto T, Watanabe H, et al: Overexpression of Rev1 promotes the development of carcinogen-induced intestinal adenomas via accumulation of point mutation and suppression of apoptosis proportionally to the Rev1 expression level. Carcinogenesis. 38:570–578. 2017. View Article : Google Scholar : PubMed/NCBI

15 

Zhu N, Zhao Y, Mi M, Lu Y, Tan Y, Fang X, Weng S and Yuan Y: REV1: A novel biomarker and potential therapeutic target for various cancers. Front Genet. 13:9979702022. View Article : Google Scholar : PubMed/NCBI

16 

Wojtaszek JL, Chatterjee N, Najeeb J, Ramos A, Lee M, Bian K, Xue JY, Fenton BA, Park H, Li D, et al: A small molecule targeting mutagenic translesion synthesis improves chemotherapy. Cell. 178:152–159.e11. 2019. View Article : Google Scholar : PubMed/NCBI

17 

Chatterjee N, Whitman MA, Harris CA, Min SM, Jonas O, Lien EC, Luengo A, Vander Heiden MG, Hong J, Zhou P, et al: REV1 inhibitor JH-RE-06 enhances tumor cell response to chemotherapy by triggering senescence hallmarks. Proc Natl Acad Sci USA. 117:28918–28921. 2020. View Article : Google Scholar : PubMed/NCBI

18 

Chen Y, Jie X, Xing B, Wu Z, Yang X, Rao X, Xu Y, Zhou D, Dong X, Zhang T, et al: REV1 promotes lung tumorigenesis by activating the Rad18/SERTAD2 axis. Cell Death Dis. 13:1102022. View Article : Google Scholar : PubMed/NCBI

19 

Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M and Gingeras TR: STAR: Ultrafast universal RNA-seq aligner. Bioinformatics. 29:15–21. 2013. View Article : Google Scholar : PubMed/NCBI

20 

Mizuno H, Kitada K, Nakai K and Sarai A: PrognoScan: A new database for meta-analysis of the prognostic value of genes. BMC Med Genomics. 2:182009. View Article : Google Scholar : PubMed/NCBI

21 

Sharma S, Shah NA, Joiner AM, Roberts KH and Canman CE: DNA polymerase ζ is a major determinant of resistance to platinum-based chemotherapeutic agents. Mol Pharmacol. 81:778–787. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, et al: Ferroptosis: An iron-dependent form of nonapoptotic cell death. Cell. 149:1060–1072. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Gao M, Monian P, Pan Q, Zhang W, Xiang J and Jiang X: Ferroptosis is an autophagic cell death process. Cell Res. 26:1021–1032. 2016. View Article : Google Scholar : PubMed/NCBI

24 

Hou W, Xie Y, Song X, Sun X, Lotze MT, Zeh HJ III, Kang R and Tang D: Autophagy promotes ferroptosis by degradation of ferritin. Autophagy. 12:1425–1428. 2016. View Article : Google Scholar : PubMed/NCBI

25 

Radulescu S, Brookes MJ, Salgueiro P, Ridgway RA, McGhee E, Anderson K, Ford SJ, Stones DH, Iqbal TH, Tselepis C and Sansom OJ: Luminal iron levels govern intestinal tumorigenesis after Apc loss in vivo. Cell Rep. 2:270–282. 2012. View Article : Google Scholar : PubMed/NCBI

26 

Hu Q, Wei W, Wu D, Huang F, Li M, Li W, Yin J, Peng Y, Lu Y, Zhao Q and Liu L: Blockade of GCH1/BH4 axis activates ferritinophagy to mitigate the resistance of colorectal cancer to erastin-induced ferroptosis. Front Cell Dev Biol. 10:8103272022. View Article : Google Scholar : PubMed/NCBI

27 

Dekker E, Tanis PJ, Vleugels JLA, Kasi PM and Wallace MB: Colorectal cancer. Lancet. 394:1467–1480. 2019. View Article : Google Scholar : PubMed/NCBI

28 

Xie K, Doles J, Hemann MT and Walker GC: Error-prone translesion synthesis mediates acquired chemoresistance. Proc Natl Acad Sci USA. 107:20792–20797. 2010. View Article : Google Scholar : PubMed/NCBI

29 

Bruno PM, Liu Y, Park GY, Murai J, Koch CE, Eisen TJ, Pritchard JR, Pommier Y, Lippard SJ and Hemann MT: A subset of platinum-containing chemotherapeutic agents kills cells by inducing ribosome biogenesis stress. Nat Med. 23:461–471. 2017. View Article : Google Scholar : PubMed/NCBI

30 

Sekimoto T, Oda T, Kurashima K, Hanaoka F and Yamashita T: Both high-fidelity replicative and low-fidelity Y-family polymerases are involved in DNA rereplication. Mol Cell Biol. 35:699–715. 2015. View Article : Google Scholar : PubMed/NCBI

31 

Wang G, Wang JJ, Zhi-Min Z, Xu XN, Shi F and Fu XL: Targeting critical pathways in ferroptosis and enhancing antitumor therapy of Platinum drugs for colorectal cancer. Sci Prog. 106:3685042211471732023. View Article : Google Scholar : PubMed/NCBI

32 

Jiang X, Stockwell BR and Conrad M: Ferroptosis: Mechanisms, biology and role in disease. Nat Rev Mol Cell Biol. 22:266–282. 2021. View Article : Google Scholar : PubMed/NCBI

33 

Fakouri NB, Durhuus JA, Regnell CE, Angleys M, Desler C, Hasan-Olive MM, Martín-Pardillos A, Tsaalbi-Shtylik A, Thomsen K, Lauritzen M, et al: Rev1 contributes to proper mitochondrial function via the PARP-NAD+-SIRT1-PGC1alpha axis. Sci Rep. 7:124802017. View Article : Google Scholar : PubMed/NCBI

34 

Anugula S, Li Z, Li Y, Hendriksen A, Christensen PB, Wang L, Monk JM, de Wind N, Bohr VA, Desler C, et al: Rev1 deficiency induces a metabolic shift in MEFs that can be manipulated by the NAD(+) precursor nicotinamide riboside. Heliyon. 9:e173922023. View Article : Google Scholar : PubMed/NCBI

35 

Federico G, Carrillo F, Dapporto F, Chiariello M, Santoro M, Bellelli R and Carlomagno F: NCOA4 links iron bioavailability to DNA metabolism. Cell Rep. 40:1112072022. View Article : Google Scholar : PubMed/NCBI

36 

Wu H, Liu Q, Shan X, Gao W and Chen Q: ATM orchestrates ferritinophagy and ferroptosis by phosphorylating NCOA4. Autophagy. 19:2062–2077. 2023. View Article : Google Scholar : PubMed/NCBI

37 

Zhang MJ, Song ML, Zhang Y, Yang XM, Lin HS, Chen WC, Zhong XD, He CY, Li T, Liu Y, et al: SNS alleviates depression-like behaviors in CUMS mice by regluating dendritic spines via NCOA4-mediated ferritinophagy. J Ethnopharmacol. 312:1163602023. View Article : Google Scholar : PubMed/NCBI

38 

Kuno S and Iwai K: Oxygen modulates iron homeostasis by switching iron sensing of NCOA4. J Biol Chem. 299:1047012023. View Article : Google Scholar : PubMed/NCBI

39 

Bellelli R, Castellone MD, Guida T, Limongello R, Dathan NA, Merolla F, Cirafici AM, Affuso A, Masai H, Costanzo V, et al: NCOA4 transcriptional coactivator inhibits activation of DNA replication origins. Mol Cell. 55:123–137. 2014. View Article : Google Scholar : PubMed/NCBI

40 

Li J, Zheng C, Mai Q, Huang X, Pan W, Lu J, Chen Z, Zhang S, Zhang C, Huang H, et al: Tyrosine catabolism enhances genotoxic chemotherapy by suppressing translesion DNA synthesis in epithelial ovarian cancer. Cell Metab. 35:2044–2059.e8. 2023. View Article : Google Scholar : PubMed/NCBI

41 

Chen Y, Feng X, Wu Z, Yang Y, Rao X, Meng R, Zhang S, Dong X, Xu S, Wu G and Jie X: USP9X-mediated REV1 deubiquitination promotes lung cancer radioresistance via the action of REV1 as a Rad18 molecular scaffold for cystathionine γ-lyase. J Biomed Sci. 31:552024. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Cheng J, Yang X, Zhao W, Xu J, Hao Y and Xu F: REV1‑targeting inhibitor JH‑RE‑06 induces ferroptosis via NCOA4‑mediated ferritinophagy in colorectal cancer cells. Oncol Rep 54: 159, 2025.
APA
Cheng, J., Yang, X., Zhao, W., Xu, J., Hao, Y., & Xu, F. (2025). REV1‑targeting inhibitor JH‑RE‑06 induces ferroptosis via NCOA4‑mediated ferritinophagy in colorectal cancer cells. Oncology Reports, 54, 159. https://doi.org/10.3892/or.2025.8992
MLA
Cheng, J., Yang, X., Zhao, W., Xu, J., Hao, Y., Xu, F."REV1‑targeting inhibitor JH‑RE‑06 induces ferroptosis via NCOA4‑mediated ferritinophagy in colorectal cancer cells". Oncology Reports 54.6 (2025): 159.
Chicago
Cheng, J., Yang, X., Zhao, W., Xu, J., Hao, Y., Xu, F."REV1‑targeting inhibitor JH‑RE‑06 induces ferroptosis via NCOA4‑mediated ferritinophagy in colorectal cancer cells". Oncology Reports 54, no. 6 (2025): 159. https://doi.org/10.3892/or.2025.8992
Copy and paste a formatted citation
x
Spandidos Publications style
Cheng J, Yang X, Zhao W, Xu J, Hao Y and Xu F: REV1‑targeting inhibitor JH‑RE‑06 induces ferroptosis via NCOA4‑mediated ferritinophagy in colorectal cancer cells. Oncol Rep 54: 159, 2025.
APA
Cheng, J., Yang, X., Zhao, W., Xu, J., Hao, Y., & Xu, F. (2025). REV1‑targeting inhibitor JH‑RE‑06 induces ferroptosis via NCOA4‑mediated ferritinophagy in colorectal cancer cells. Oncology Reports, 54, 159. https://doi.org/10.3892/or.2025.8992
MLA
Cheng, J., Yang, X., Zhao, W., Xu, J., Hao, Y., Xu, F."REV1‑targeting inhibitor JH‑RE‑06 induces ferroptosis via NCOA4‑mediated ferritinophagy in colorectal cancer cells". Oncology Reports 54.6 (2025): 159.
Chicago
Cheng, J., Yang, X., Zhao, W., Xu, J., Hao, Y., Xu, F."REV1‑targeting inhibitor JH‑RE‑06 induces ferroptosis via NCOA4‑mediated ferritinophagy in colorectal cancer cells". Oncology Reports 54, no. 6 (2025): 159. https://doi.org/10.3892/or.2025.8992
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