{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T10:22:16Z","timestamp":1768386136813,"version":"3.49.0"},"reference-count":57,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81603418"],"award-info":[{"award-number":["81603418"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Central Government Funding Program for Local University Reform","award":["2020YQ05"],"award-info":[{"award-number":["2020YQ05"]}]},{"name":"Heilongjiang Touyan Innovation Team Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The development of RNA-based drugs for MAFLD-related fibrosis is severely hampered by the poor oral bioavailability of nucleic acids. This study employed a novel, patent-protected LNP formulation to orally deliver plant-derived miR-55 and investigate its therapeutic potential, focusing on its novel mechanism of action via the CK2\u03b1\/SMO interaction. In a rat model established with a methionine-choline-deficient diet, orally administered miR-55 markedly improved liver injury, lipid dysregulation, oxidative stress, and pathological collagen deposition. The anti-fibrotic efficacy was quantitatively confirmed by a significant reduction in hepatic hydroxyproline content and downregulation of key fibrogenic genes (Col1a1, Col3a1, TIMP-1, TGF-\u03b21, CTGF) and pro-inflammatory cytokines (TNF-\u03b1, IL-6), achieving effects comparable to the full Ge Xia Zhu Yu Decoction. Mechanistically, both bioinformatic prediction and in vivo validation indicated that miR-55 is predicted to target CK2\u03b1. This targeting suppressed CK2\u03b1 expression and disrupted the endogenous CK2\u03b1-SMO complex, thereby promoting the ubiquitin-mediated degradation of SMO\u2014a previously unreported mechanism. This cascade inhibited the downstream Gli1 pathway and downregulated pro-fibrotic and pro-angiogenic factors (VEGF, PDGF), thereby providing a comprehensive mechanistic basis for the therapeutic effects. This study is the first to provide evidence that orally delivered, plant-derived miR-55 may act as a natural modulator that potentially through disrupting the CK2\u03b1\/SMO interaction via a unique complex disruption-promoted degradation mechanism, attenuating Hedgehog signaling and alleviating liver fibrosis. These findings offer important insights into cross-kingdom regulation and highlight miR-55 as a potential targeted therapeutic candidate.<\/jats:p>","DOI":"10.3390\/ijms27020748","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T09:13:01Z","timestamp":1768209181000},"page":"748","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plant-Derived miR-55 Alleviates Liver Fibrosis by Disrupting the CK2\u03b1\/SMO Complex and Promoting SMO Ubiquitination"],"prefix":"10.3390","volume":"27","author":[{"given":"Lei","family":"Wu","sequence":"first","affiliation":[{"name":"College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Basic Medical Science, Heilongjiang University of Chinese Medicine, Harbin 150040, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anqi","family":"Li","sequence":"additional","affiliation":[{"name":"College of Biomedicine and Health, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuqiang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Basic Medical Science, Heilongjiang University of Chinese Medicine, Harbin 150040, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenbo","family":"Li","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yihan","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Tang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, China"},{"name":"Key Laboratory of Basic and Application Research of Beiyao, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin 150040, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.jhep.2020.03.039","article-title":"A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement","volume":"73","author":"Eslam","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00423-020-01965-1","article-title":"Mechanisms of nonalcoholic fatty liver disease and implications for surgery","volume":"406","author":"Kaufmann","year":"2021","journal-title":"Langenbecks Arch. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1053\/j.gastro.2019.11.312","article-title":"MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease","volume":"158","author":"Eslam","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Roehlen, N., Crouchet, E., and Baumert, T.F. (2020). Liver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives. Cells, 9.","DOI":"10.3390\/cells9040875"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1111\/febs.13665","article-title":"TGF-\u03b2 signalling and liver disease","volume":"283","author":"Fabregat","year":"2016","journal-title":"FEBS J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"111556","DOI":"10.1016\/j.fct.2020.111556","article-title":"The liver fibrosis niche: Novel insights into the interplay between fibrosis-composing mesenchymal cells, immune cells, endothelial cells, and extracellular matrix","volume":"143","author":"Matsuda","year":"2020","journal-title":"Food Chem. Toxicol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/S2468-1253(16)30110-8","article-title":"Antifibrotics in chronic liver disease: Tractable targets and translational challenges","volume":"1","author":"Ramachandran","year":"2016","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Lei, L., Ei Mourabit, H., Housset, C., Cadoret, A., and Lemoinne, S. (2021). Role of Angiogenesis in the Pathogenesis of NAFLD. J. Clin. Med., 10.","DOI":"10.3390\/jcm10071338"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Caligiuri, A., Gentilini, A., Pastore, M., Gitto, S., and Marra, F. (2021). Cellular and Molecular Mechanisms Underlying Liver Fibrosis Regression. Cells, 10.","DOI":"10.3390\/cells10102759"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Chojnowski, J.E., Li, R., Tsang, T., Alfaran, F.H., Dick, A., Cocklin, S., Brady, D.C., and Strochlic, T.I. (2022). Copper modulates the catalytic activity of protein kinase CK2. Front. Mol. Biosci., 9.","DOI":"10.3389\/fmolb.2022.878652"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.hbpd.2021.09.003","article-title":"CK2\u03b1 causes stemness and chemotherapy resistance in liver cancer through the Hedgehog signaling pathway","volume":"22","author":"Wu","year":"2023","journal-title":"Hepatobiliary Pancreat. Dis. Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1111\/bph.15945","article-title":"CK2 blockade alleviates liver fibrosis by suppressing activation of hepatic stellate cells via the Hedgehog pathway","volume":"180","author":"Fan","year":"2022","journal-title":"Br. J. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/s41575-018-0009-6","article-title":"Triggering and resolution of inflammation in NASH","volume":"15","author":"Schuster","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1172\/JCI88881","article-title":"Liver inflammation and fibrosis","volume":"127","author":"Koyama","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"109965","DOI":"10.1016\/j.plaphy.2025.109965","article-title":"Unravelling the interplay between plant miRNAs and plant secondary metabolites: A new frontier in cross-kingdom regulatory mechanisms","volume":"225","author":"Agarwal","year":"2025","journal-title":"Plant Physiol. Biochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"144079","DOI":"10.1016\/j.ijbiomac.2025.144079","article-title":"Immunoregulatory mechanisms and cross-kingdom bacteriostatic effects of microRNAs in crustacean","volume":"311","author":"Sun","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.tifs.2021.10.032","article-title":"Inter-kingdom regulation of human transcriptome by dietary microRNAs: Emerging bioactives from edible plants to treat human diseases?","volume":"118","author":"Kalarikkal","year":"2021","journal-title":"Trends Food Sci. Technol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1007\/s11095-022-03459-9","article-title":"SNAC for enhanced oral bioavailability: An updated review","volume":"40","author":"Kommineni","year":"2022","journal-title":"Pharm. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/cr.2011.158","article-title":"Exogenous Plant MIR168a Specifically Targets Mammalian LDLRAP1: Evidence of Cross-Kingdom Regulation by MicroRNA","volume":"22","author":"Zhang","year":"2011","journal-title":"Cell Res."},{"key":"ref_20","unstructured":"Wang, R., Yang, J., Zhang, J.H., Zhang, B.B., and Zhao, Y.W. (2024). A miR-55 Preparation, Its Preparation Method and Application. (Chinese Patent ZL202211446002.4)."},{"key":"ref_21","unstructured":"Yang, J., Wang, R., Zhang, J.H., Zhao, Y.W., and Zhang, B.B. (2024). Application of miR-55 in Inhibiting Nonalcoholic Fatty Liver Fibrosis. (Chinese Patent ZL202211445995.3)."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2303261","DOI":"10.1002\/adma.202303261","article-title":"Lipid Nanoparticle (LNP) Enables mRNA Delivery for Cancer Therapy","volume":"35","author":"Zong","year":"2023","journal-title":"Adv. Mater."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1038\/s41565-019-0591-y","article-title":"The Onpattro Story and the Clinical Translation of Nanomedicines Containing Nucleic Acid-Based Drugs","volume":"14","author":"Akinc","year":"2019","journal-title":"Nat. Nanotechnol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"9549","DOI":"10.1039\/D1FO01156A","article-title":"Cross-kingdom regulation by dietary plant miRNAs: An evidence-based review with recent updates","volume":"12","author":"Jia","year":"2021","journal-title":"Food Funct."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4316","DOI":"10.1021\/acs.jafc.1c07730","article-title":"Digestion of plant dietary miRNAs starts in the mouth under the protection of coingested food components and plant-derived exosome-like nanoparticles","volume":"70","author":"Qin","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.jep.2012.06.005","article-title":"A Chinese herbal medicine, Gexia-Zhuyu Tang (GZT), prevents dimethylnitrosamine-induced liver fibrosis through inhibition of hepatic stellate cells proliferation","volume":"142","author":"Chen","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"100610","DOI":"10.1016\/j.cjac.2025.100610","article-title":"Gexia Zhuyu Decoction alleviates carbon tetrachloride-induced hepatic fibrosis in mice: Mechanistic insights from integrated network analysis and experimental validation","volume":"53","author":"Xu","year":"2025","journal-title":"Chin. J. Anal. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2835","DOI":"10.12659\/MSM.913481","article-title":"Gexia-Zhuyu Decoction attenuates carbon tetrachloride-induced liver fibrosis in mice partly via liver angiogenesis mediated by myeloid cells","volume":"25","author":"Deng","year":"2019","journal-title":"Med. Sci. Monit."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.4161\/rna.22034","article-title":"Mechanisms that impact microRNA stability in plants","volume":"9","author":"Zhao","year":"2012","journal-title":"RNA Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"eaau6977","DOI":"10.1126\/science.aau6977","article-title":"The biology, function, and biomedical applications of exosomes","volume":"367","author":"Kalluri","year":"2020","journal-title":"Science"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1016\/S2210-7401(11)70003-1","article-title":"Liver fibrogenesis and metabolic factors","volume":"35","author":"Anty","year":"2011","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/s41586-019-1631-3","article-title":"Resolving the fibrotic niche of human liver cirrhosis at single-cell level","volume":"575","author":"Ramachandran","year":"2019","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Veskovi\u0107, M., Pejovi\u0107, M., \u0160utulovi\u0107, N., Hrn\u010di\u0107, D., Ra\u0161i\u0107-Markovi\u0107, A., Stanojlovi\u0107, O., and Mladenovi\u0107, D. (2024). Exploring fibrosis pathophysiology in lean and obese metabolic-associated fatty liver disease: An in-depth comparison. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25137405"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"111532","DOI":"10.1016\/j.biopha.2021.111532","article-title":"FTZ attenuates liver steatosis and fibrosis in the minipigs with type 2 diabetes by regulating the AMPK signaling pathway","volume":"138","author":"Wang","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"108888","DOI":"10.1016\/j.jnutbio.2021.108888","article-title":"Nobiletin mitigates hepatocytes death, liver inflammation, and fibrosis in a murine model of NASH through modulating hepatic oxidative stress and mitochondrial dysfunction","volume":"100","author":"Li","year":"2022","journal-title":"J. Nutr. Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1002\/hep.32285","article-title":"Hepatic Fibrosis 2022: Unmet Needs and a Blueprint for the Future","volume":"75","author":"Friedman","year":"2022","journal-title":"Hepatology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3821","DOI":"10.1111\/jcmm.13304","article-title":"MMP-13 deletion decreases profibrogenic molecules and attenuates N nitrosodimethylamine-induced liver injury and fibrosis in mice","volume":"21","author":"George","year":"2017","journal-title":"J. Cell. Mol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Hu, Z., Yue, H., Jiang, N., and Qiao, L. (2025). Diet, oxidative stress and MAFLD: A mini review. Front. Nutr., 12.","DOI":"10.3389\/fnut.2025.1539578"},{"key":"ref_39","first-page":"1","article-title":"Metabolic dysfunction-associated steatotic liver disease-induced changes in the antioxidant system: A review","volume":"99","year":"2024","journal-title":"Arch. Toxicol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.7150\/ijbs.92749","article-title":"Oxidative stress promotes liver fibrosis by modulating the microRNA-144 and SIN3A-p38 pathways in hepatic stellate cells","volume":"20","author":"Hao","year":"2024","journal-title":"Int. J. Biol. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"114014","DOI":"10.1016\/j.biopha.2022.114014","article-title":"The phenolic compounds tyrosol and hydroxytyrosol counteract liver fibrogenesis via the transcriptional modulation of NADPH oxidases and oxidative stress-related miRNAs","volume":"157","author":"Gabbia","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3456","DOI":"10.7150\/ijbs.80760","article-title":"MiR-552-3p regulates multiple fibrotic and inflammatory genes concurrently in hepatic stellate cells improving NASH-associated phenotypes","volume":"19","author":"Ma","year":"2023","journal-title":"Int. J. Biol. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.addr.2020.06.002","article-title":"Lipid Nanoparticles for Nucleic Acid Delivery: Current Perspectives","volume":"154\u2013155","author":"Samaridou","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.addr.2020.06.026","article-title":"Lipid Nanoparticle Technology for Therapeutic Gene Regulation in the Liver","volume":"159","author":"Witzigmann","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"8635329","DOI":"10.1155\/2018\/8635329","article-title":"Investigating pathogenic and hepatocarcinogenic mechanisms from normal liver to HCC by constructing genetic and epigenetic networks via big genetic and epigenetic data mining and genome-wide NGS data identification","volume":"2018","author":"Li","year":"2018","journal-title":"Dis. Markers"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2256","DOI":"10.1111\/liv.15682","article-title":"miR-21-5p promotes NASH-related hepatocarcinogenesis","volume":"43","author":"Rodrigues","year":"2023","journal-title":"Liver Int."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Liu, Y.C., Chen, W.L., Kung, W.H., and Huang, H.D. (2017). Plant miRNAs found in human circulating system provide evidences of cross kingdom RNAi. BMC Genom., 18.","DOI":"10.1186\/s12864-017-3502-3"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Tan, H., Wang, C., Li, F., Peng, Y., Sima, J., Li, Y., Deng, L., Wu, K., Xu, Z., and Zhang, Z. (2025). Cross-kingdom regulation of gene expression in giant pandas via plant-derived miRNA. Front. Vet. Sci., 12.","DOI":"10.3389\/fvets.2025.1509698"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s12935-024-03215-6","article-title":"Modified Gexia-Zhuyu Tang inhibits gastric cancer progression by restoring gut microbiota and regulating pyroptosis","volume":"24","author":"Zhao","year":"2024","journal-title":"Cancer Cell Int."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Chu, X., Liu, S., Qu, B., Xin, Y., and Lu, L. (2024). Salidroside may target PPAR\u03b1 to exert preventive and therapeutic activities on NASH. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1433076"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"13","DOI":"10.4103\/1477-3163.55429","article-title":"Gli1 maintains cell survival by up-regulating IGFBP6 and Bcl-2 through promoter regions in parallel manner in pancreatic cancer cells","volume":"8","author":"Wang","year":"2009","journal-title":"J. Carcinog."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s10549-009-0423-0","article-title":"The hedgehog pathway as a therapeutic target for treatment of breast cancer","volume":"116","author":"Barginear","year":"2009","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.cell.2012.01.021","article-title":"Hypoxia-Inducible Factors in Physiology and Medicine","volume":"148","author":"Semenza","year":"2012","journal-title":"Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"47","DOI":"10.2478\/s11658-012-0037-0","article-title":"Regulation of Angiogenesis by Hypoxia: The Role of MicroRNA","volume":"18","author":"Madanecki","year":"2013","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1261\/rna.5248604","article-title":"Fast and effective prediction of microRNA\/target duplexes","volume":"10","author":"Rehmsmeier","year":"2004","journal-title":"RNA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"W451","DOI":"10.1093\/nar\/gkl243","article-title":"RNAhybrid: MicroRNA target prediction easy, fast and flexible","volume":"34","author":"Rehmsmeier","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"37218","DOI":"10.1074\/jbc.M110.174565","article-title":"Casein kinase 2 promotes Hedgehog signaling by regulating both smoothened and Cubitus interruptus","volume":"285","author":"Jia","year":"2010","journal-title":"J. Biol. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/748\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T05:17:12Z","timestamp":1768367832000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/748"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,12]]},"references-count":57,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["ijms27020748"],"URL":"https:\/\/doi.org\/10.3390\/ijms27020748","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,12]]}}}