{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:02:28Z","timestamp":1787068948867,"version":"build-2736575974"},"reference-count":55,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Grants Council","award":["17106824"],"award-info":[{"award-number":["17106824"]}]},{"name":"Research Grants Council","award":["202010160029"],"award-info":[{"award-number":["202010160029"]}]},{"name":"Research Grants Council","award":["202111160035"],"award-info":[{"award-number":["202111160035"]}]},{"name":"Research Grants Council","award":["2303101663"],"award-info":[{"award-number":["2303101663"]}]},{"name":"Research Grants Council","award":["2302101666"],"award-info":[{"award-number":["2302101666"]}]},{"name":"Committee on Research and Conference Grants from the University of Hong Kong","award":["17106824"],"award-info":[{"award-number":["17106824"]}]},{"name":"Committee on Research and Conference Grants from the University of Hong Kong","award":["202010160029"],"award-info":[{"award-number":["202010160029"]}]},{"name":"Committee on Research and Conference Grants from the University of Hong Kong","award":["202111160035"],"award-info":[{"award-number":["202111160035"]}]},{"name":"Committee on Research and Conference Grants from the University of Hong Kong","award":["2303101663"],"award-info":[{"award-number":["2303101663"]}]},{"name":"Committee on Research and Conference Grants from the University of Hong Kong","award":["2302101666"],"award-info":[{"award-number":["2302101666"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>BQ323636.1 (BQ) is a splice variant of NCOR2. Its overexpression is associated with endocrine therapy and chemoresistance in estrogen receptor-positive (ER+ve) breast cancer. This study investigates how BQ overexpression drives doxorubicin (DOX) resistance by enhancing androgen receptor (AR) signaling and non-homologous end joining (NHEJ). BQ overexpressed breast cancer cell lines (MCF-7, T-47D, BT-549, MDA-MB-453), showed increased AR activity (ARE-luciferase assay) and demonstrated DOX resistance (EC50 &gt; 10-fold with DHT, p &lt; 0.05), as assessed via cell viability, TUNEL, and comet assays. RNA-sequencing (GSE295979, GSE2048) revealed the involvement of AR signaling. BQ upregulated cell cycle-related kinase (CCRK), stabilizing KU70, a key NHEJ protein, resulting in enhanced NHEJ activity (EJ5-GFP assay, p &lt; 0.01). Co-immunoprecipitation confirmed the interaction between CCRK and KU70, and CCRK was found to modulate the protein stability of KU70. AR inhibition with bicalutamide in BQ overexpressing cells reversed DOX resistance. Xenograft models validated AR-dependent DOX resistance. In ER+ve breast cancer patient samples, high CCRK expression correlated with DOX resistance (p = 0.002) and metastasis (p = 0.001). Kaplan\u2013Meier analysis showed poorer overall survival (p &lt; 0.001) and disease-specific survival (p &lt; 0.001) in cancers with high CCRK. Cox-regression analysis showed that high CCRK was a poorer prognostic factor of overall survival (p &lt; 0.001; RR 3.056, 95% CI 1.661, 5.621, AR (p &lt; 0.001; RR 3.420, 95% CI 1.783, 6.562), and disease-specific survival (p &lt; 0.001; RR 2.731, 95% CI 1.472, 5.067). The BQ-AR-CCRK-KU70 axis represents a novel mechanism of DOX resistance in ER+ve breast cancer, suggesting AR or CCRK inhibition as a potential therapeutic strategy.<\/jats:p>","DOI":"10.3390\/cells14171341","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T16:18:15Z","timestamp":1756484295000},"page":"1341","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["BQ323636.1 Employs the AR-CCRK Axis to Modulate the Expression of KU70 to Interfere with Non-Homologous End Joining Mediated DNA Repair Mechanism"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2037-9575","authenticated-orcid":false,"given":"Ho","family":"Tsoi","sequence":"first","affiliation":[{"name":"Department of Pathology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Qing","family":"So","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2435-6646","authenticated-orcid":false,"given":"Ellen P. S.","family":"Man","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan-Ping","family":"You","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koei Ho-Lam","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin-Suen","family":"Tse","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9793-9273","authenticated-orcid":false,"given":"Wing-Lok","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2200-7505","authenticated-orcid":false,"given":"Ui-Soon","family":"Khoo","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1111\/cge.13900","article-title":"Molecular intrinsic versus clinical subtyping in breast cancer: A comprehensive review","volume":"99","author":"Szymiczek","year":"2021","journal-title":"Clin. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100067","DOI":"10.1016\/j.xgen.2021.100067","article-title":"Molecular analysis of TCGA breast cancer histologic types","volume":"1","author":"Thennavan","year":"2021","journal-title":"Cell Genom."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1200\/JCO.20.00853","article-title":"Molecular Drivers of Oncotype DX, Prosigna, EndoPredict, and the Breast Cancer Index: A TransATAC Study","volume":"39","author":"Buus","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1001\/jama.2018.19323","article-title":"Breast Cancer Treatment: A Review","volume":"321","author":"Waks","year":"2019","journal-title":"JAMA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.annonc.2020.01.008","article-title":"Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with early breast cancer: A KSMO-ESMO initiative endorsed by CSCO, ISMPO, JSMO, MOS, SSO and TOS","volume":"31","author":"Park","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/s41586-019-1730-1","article-title":"A view on drug resistance in cancer","volume":"575","author":"Vasan","year":"2019","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"12910","DOI":"10.1038\/ncomms12910","article-title":"Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration","volume":"7","author":"Smid","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e12118","DOI":"10.15252\/emmm.202012118","article-title":"The mutational landscape of the SCAN-B real-world primary breast cancer transcriptome","volume":"12","author":"Brueffer","year":"2020","journal-title":"Embo Mol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s10549-018-4753-7","article-title":"Mutant p53 in breast cancer: Potential as a therapeutic target and biomarker","volume":"170","author":"Duffy","year":"2018","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"111","DOI":"10.2147\/BCTT.S60696","article-title":"PI3K mutations in breast cancer: Prognostic and therapeutic implications","volume":"7","author":"Mukohara","year":"2015","journal-title":"Breast Cancer-Target"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Martorana, F., Motta, G., Pavone, G., Motta, L., Stella, S., Vitale, S.R., Manzella, L., and Vigneri, P. (2021). AKT Inhibitors: New Weapons in the Fight Against Breast Cancer?. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.662232"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1038\/s41419-020-02998-6","article-title":"PI3K\/AKT pathway as a key link modulates the multidrug resistance of cancers","volume":"11","author":"Liu","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Dong, C., Wu, J., Chen, Y., Nie, J.N., and Chen, C.S. (2021). Activation of PI3K\/AKT\/mTOR Pathway Causes Drug Resistance in Breast Cancer. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.628690"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"eaaw4993","DOI":"10.1126\/scitranslmed.aaw4993","article-title":"The androgen receptor regulates a druggable translational regulon in advanced prostate cancer","volume":"11","author":"Liu","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Obinata, D., Lawrence, M.G., Takayama, K., Choo, N., Risbridger, G.P., Takahashi, S., and Inoue, S. (2020). Recent Discoveries in the Androgen Receptor Pathway in Castration-Resistant Prostate Cancer. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.581515"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41391-019-0153-2","article-title":"Role of the DNA damage response in prostate cancer formation, progression and treatment","volume":"23","author":"Zhang","year":"2020","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1158\/2159-8290.CD-13-0172","article-title":"Androgen Receptor Signaling Regulates DNA Repair in Prostate Cancers","volume":"3","author":"Polkinghorn","year":"2013","journal-title":"Cancer Discov."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/jcp.25048","article-title":"Mechanisms and Consequences of Double-Strand DNA Break Formation in Chromatin","volume":"231","author":"Cannan","year":"2016","journal-title":"J. Cell Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Li, L.Y., Guan, Y.D., Chen, X.S., Yang, J.M., and Cheng, Y. (2021). DNA Repair Pathways in Cancer Therapy and Resistance. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.629266"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.pbiomolbio.2014.12.003","article-title":"The DNA-dependent protein kinase: A multifunctional protein kinase with roles in DNA double strand break repair and mitosis","volume":"117","author":"Jette","year":"2015","journal-title":"Prog. Biophys. Mol. Bio."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e98096","DOI":"10.1172\/jci.insight.98096","article-title":"Temporal DNA-PK activation drives genomic instability and therapy resistance in glioma stem cells","volume":"3","author":"Wang","year":"2018","journal-title":"JCI Insight"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"eaam7479","DOI":"10.1126\/scisignal.aam7479","article-title":"Androgen receptor inhibitor-induced \u201cBRCAness\u201d and PARP inhibition are synthetically lethal for castration-resistant prostate cancer","volume":"10","author":"Li","year":"2017","journal-title":"Sci. Signal"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/s41467-017-00393-y","article-title":"Synthetic lethality between androgen receptor signalling and the PARP pathway in prostate cancer","volume":"8","author":"Asim","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4245","DOI":"10.1172\/JCI127613","article-title":"Supraphysiological androgens suppress prostate cancer growth through androgen receptor-mediated DNA damage","volume":"129","author":"Chatterjee","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Chen, M.Y., Yang, Y.B., Xu, K., Li, L.L., Huang, J., and Qiu, F.M. (2020). Androgen Receptor in Breast Cancer: From Bench to Bedside. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.00573"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1158\/1078-0432.CCR-10-2021","article-title":"Androgen Receptor Expression and Breast Cancer Survival in Postmenopausal Women","volume":"17","author":"Hu","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s13058-019-1118-z","article-title":"Prognostic and predictive value of androgen receptor expression in postmenopausal women with estrogen receptor-positive breast cancer: Results from the Breast International Group Trial 1-98","volume":"21","author":"Kensler","year":"2019","journal-title":"Breast Cancer Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/s41591-020-01168-7","article-title":"The androgen receptor is a tumor suppressor in estrogen receptor-positive breast cancer","volume":"27","author":"Hickey","year":"2021","journal-title":"Nat. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.ccr.2011.05.026","article-title":"Targeting Androgen Receptor in Estrogen Receptor-Negative Breast Cancer","volume":"20","author":"Ni","year":"2011","journal-title":"Cancer Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1158\/0008-5472.CAN-12-2241","article-title":"SpliceArray profiling of breast cancer reveals a novel variant of NCOR2\/SMRT that is associated with tamoxifen resistance and control of ERalpha transcriptional activity","volume":"73","author":"Zhang","year":"2013","journal-title":"Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3681","DOI":"10.1158\/1078-0432.CCR-17-2259","article-title":"BQ323636.1, a Novel Splice Variant to NCOR2, as a Predictor for Tamoxifen-Resistant Breast Cancer","volume":"24","author":"Gong","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1002\/path.6157","article-title":"Overexpression of BQ323636.1 contributes to anastrozole resistance in AR+ve\/ER+ve breast cancer","volume":"261","author":"Tsoi","year":"2023","journal-title":"J. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Leung, M.H., Tsoi, H., Gong, C., Man, E.P., Zona, S., Yao, S., Lam, E.W., and Khoo, U.S. (2020). A Splice Variant of NCOR2, BQ323636.1, Confers Chemoresistance in Breast Cancer by Altering the Activity of NRF2. Cancers, 12.","DOI":"10.3390\/cancers12030533"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Gyori, B.M., Venkatachalam, G., Thiagarajan, P.S., Hsu, D., and Clement, M.V. (2021). Corrigendum to OpenComet: An automated tool for comet assay image analysis [Redox Biol. Volume 2, 2014, Pages 457\u2013465]. Redox Biol., 40.","DOI":"10.1016\/j.redox.2021.101876"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2633","DOI":"10.1101\/gad.13.20.2633","article-title":"XRCC3 promotes homology-directed repair of DNA damage in mammalian cells","volume":"13","author":"Pierce","year":"1999","journal-title":"Genes. Dev."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Bennardo, N., Gunn, A., Cheng, A., Hasty, P., and Stark, J.M. (2009). Limiting the persistence of a chromosome break diminishes its mutagenic potential. PLoS Genet., 5.","DOI":"10.1371\/journal.pgen.1000683"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3831","DOI":"10.1101\/gad.12.24.3831","article-title":"Double-strand break repair by interchromosomal recombination: Suppression of chromosomal translocations","volume":"12","author":"Richardson","year":"1998","journal-title":"Genes. Dev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1590\/S0100-879X2006000800013","article-title":"Gene expression profiling of clinical stages II and III breast cancer","volume":"39","author":"Folgueira","year":"2006","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Tsoi, H., You, C.-P., Cheung, K.H.-L., Tse, Y.-S., and Khoo, U.-S. (2025). The Splice Variant of the NCOR2 Gene BQ323636.1 Modulates ACSL4 Expression to Enhance Fatty Acid Metabolism and Support of Tumor Growth in Breast Cancer. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26114989"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Ge, S.X., Son, E.W., and Yao, R. (2018). iDEP: An integrated web application for differential expression and pathway analysis of RNA-Seq data. BMC Bioinform., 19.","DOI":"10.1186\/s12859-018-2486-6"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"D672","DOI":"10.1093\/nar\/gkae909","article-title":"KEGG: Biological systems database as a model of the real world","volume":"53","author":"Kanehisa","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Yu, B., Liu, Y., Luo, H., Fu, J., Li, Y., and Shao, C. (2021). Androgen receptor splicing variant 7 (ARV7) inhibits docetaxel sensitivity by inactivating the spindle assembly checkpoint. J. Biol. Chem., 296.","DOI":"10.1016\/j.jbc.2021.100276"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e22495","DOI":"10.1096\/fj.202200190R","article-title":"Androgen receptor splicing variant 7 (ARv7) promotes DNA damage response in prostate cancer cells","volume":"36","author":"Luo","year":"2022","journal-title":"FASEB J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s13073-025-01488-8","article-title":"DNA repair and the contribution to chemotherapy resistance","volume":"17","author":"Nesic","year":"2025","journal-title":"Genome Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.sbi.2020.10.010","article-title":"Mechanisms of substrate recognition by the 26S proteasome","volume":"67","author":"Davis","year":"2021","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41514-024-00135-7","article-title":"A review of the pathophysiological mechanisms of doxorubicin-induced cardiotoxicity and aging","volume":"10","author":"Linders","year":"2024","journal-title":"npj Aging"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1093\/annonc\/mdn781","article-title":"Phase III trial of doxorubicin plus cyclophosphamide (AC), docetaxel, and alternating AC and docetaxel as front-line chemotherapy for metastatic breast cancer: Japan Clinical Oncology Group trial (JCOG9802)","volume":"20","author":"Katsumata","year":"2009","journal-title":"Ann. Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/s12943-025-02339-1","article-title":"Death-ision: The link between cellular resilience and cancer resistance to treatments","volume":"24","author":"Baldassarre","year":"2025","journal-title":"Mol. Cancer"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Khoo, U.S., Man, E.P.S., So, Z.Q., and Tsoi, H. (2024, January 23\u201325). BQ323636.1 modulates the AR-CDK20 axis to confer doxorubicin resistance in breast cancer (ENA24-0047). Proceedings of the 36th EORTC-NCI-AACR Symposium, Barcelona, Spain.","DOI":"10.1016\/j.ejca.2024.114815"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1016\/j.molmed.2025.01.006","article-title":"The emerging regulatory interface between DNA repair and steroid hormone receptors in cancer","volume":"31","author":"Eickhoff","year":"2025","journal-title":"Trends Mol. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1200\/JCO.2017.75.7310","article-title":"Targeting Androgen Receptor and DNA Repair in Metastatic Castration-Resistant Prostate Cancer: Results from NCI 9012","volume":"36","author":"Hussain","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5214","DOI":"10.1038\/s41467-018-07402-8","article-title":"An inflammatory-CCRK circuitry drives mTORC1-dependent metabolic and immunosuppressive reprogramming in obesity-associated hepatocellular carcinoma","volume":"9","author":"Sun","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1038\/s41423-020-00534-2","article-title":"Cell cycle-related kinase reprograms the liver immune microenvironment to promote cancer metastasis","volume":"18","author":"Zeng","year":"2021","journal-title":"Cell Mol. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3159","DOI":"10.1172\/JCI45967","article-title":"Cell cycle-related kinase is a direct androgen receptor-regulated gene that drives beta-catenin\/T cell factor-dependent hepatocarcinogenesis","volume":"121","author":"Feng","year":"2011","journal-title":"J. Clin. Investig."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/17\/1341\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:35:23Z","timestamp":1760034923000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/17\/1341"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,29]]},"references-count":55,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["cells14171341"],"URL":"https:\/\/doi.org\/10.3390\/cells14171341","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,29]]}}}