{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T03:04:06Z","timestamp":1740107046834,"version":"3.37.3"},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T00:00:00Z","timestamp":1715212800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T00:00:00Z","timestamp":1715212800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"the startup funding of the First Affiliated Hospital of Harbin Medical University","award":["RC-GCC2021-001"],"award-info":[{"award-number":["RC-GCC2021-001"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["Grant No. 82170164"],"award-info":[{"award-number":["Grant No. 82170164"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Cancer Res Clin Oncol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Ribosomal RNA Processing 8 (RRP8) is a nucleolar Rossman fold-like methyltransferase that exhibits increased expression in many malignant tumours. However, the role of RRP8 in hepatocellular carcinoma (HCC) is still uncertain. We explored the relationships between RRP8 and prognosis and immune infiltration, as well as the putative pathological function and mechanism of RRP8 in HCC.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Analysis of RRP8 expression across cancers was performed by using multiple databases. Associations between RRP8 expression and clinicopathological factors were further examined. Gene enrichment analysis was used to identify various putative biological activities and regulatory networks of RRP8 in HCC. The relationship between RRP8 expression and immune infiltration was confirmed by single-sample gene set enrichment analysis (ssGSEA). Univariate and multivariate Cox regression analyses were conducted to assess the impact of clinical variables on patient outcomes. Furthermore, a nomogram was constructed to estimate survival probability based on multivariate Cox regression analysis. Functional validation of RRP8 in HCC was performed with two different systems: doxycycline-inducible shRNA knockdown and CRISPR-Cas9 knockout.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>RRP8 was markedly overexpressed in HCC clinical specimens compared to adjacent normal tissues. Further analysis demonstrated that RRP8 was directly connected to multiple clinical characteristics and strongly associated with various immune markers in HCC. Moreover, elevated RRP8 expression indicated an unfavourable prognosis. Our functional studies revealed that both knockdown and knockout of RRP8 dramatically attenuated liver cancer cells to proliferate and migrate. Knockout of RRP8 decreased the phosphorylation of MEK1\/2 and \u03b2-catenin-(Y654) signalling pathway components; downregulated downstream signalling effectors, including Cyclin D1 and N-cadherin; and upregulated E-cadherin.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>RRP8 is strongly implicated in immune infiltration and could be a potential therapeutic target in HCC.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00432-024-05756-9","type":"journal-article","created":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T08:01:51Z","timestamp":1715241711000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["RRP8, associated with immune infiltration, is a prospective therapeutic target in hepatocellular carcinoma"],"prefix":"10.1007","volume":"150","author":[{"given":"Kai","family":"You","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingxing","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunzheng","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fukai","family":"Wen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaoyang","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huitao","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,5,9]]},"reference":[{"issue":"7090","key":"5756_CR1","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/nature04753","volume":"441","author":"E Bettelli","year":"2006","unstructured":"Bettelli E, Carrier Y, Gao W et al (2006) Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441(7090):235\u2013238. https:\/\/doi.org\/10.1038\/nature04753","journal-title":"Nature"},{"issue":"4","key":"5756_CR2","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1016\/j.immuni.2013.10.003","volume":"39","author":"G Bindea","year":"2013","unstructured":"Bindea G, Mlecnik B, Tosolini M et al (2013) Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer. Immunity 39(4):782\u2013795. https:\/\/doi.org\/10.1016\/j.immuni.2013.10.003","journal-title":"Immunity"},{"issue":"2","key":"5756_CR3","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1016\/j.cell.2018.03.059","volume":"173","author":"A Blum","year":"2018","unstructured":"Blum A, Wang P, Zenklusen JC (2018) SnapShot: TCGA-analyzed tumors. Cell 173(2):530","journal-title":"Cell"},{"issue":"6","key":"5756_CR4","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1017\/s1355838200992288","volume":"6","author":"C Bousquet-Antonelli","year":"2000","unstructured":"Bousquet-Antonelli C, Vanrobays E, G\u00c9Lugne J-P, et al (2000) Rrp8p is a yeast nucleolar protein functionally linked to Gar1p and involved in pre-rRNA cleavage at site A2. RNA 6(6):826\u2013843. https:\/\/doi.org\/10.1017\/s1355838200992288","journal-title":"RNA"},{"issue":"4","key":"5756_CR5","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1053\/j.gastro.2015.12.041","volume":"150","author":"J Bruix","year":"2016","unstructured":"Bruix J, Reig M, Sherman M (2016) Evidence-based diagnosis, staging, and treatment of patients with hepatocellular carcinoma. Gastroenterology 150(4):835\u2013853. https:\/\/doi.org\/10.1053\/j.gastro.2015.12.041","journal-title":"Gastroenterology"},{"issue":"6","key":"5756_CR6","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1189\/jlb.0506297","volume":"80","author":"A Budhu","year":"2006","unstructured":"Budhu A, Wang XW (2006) The role of cytokines in hepatocellular carcinoma. J Leukoc Biol 80(6):1197\u20131213. https:\/\/doi.org\/10.1189\/jlb.0506297","journal-title":"J Leukoc Biol"},{"issue":"15","key":"5756_CR7","doi-asserted-by":"publisher","first-page":"5664","DOI":"10.1073\/pnas.1319051111","volume":"111","author":"SH Chang","year":"2014","unstructured":"Chang SH, Mirabolfathinejad SG, Katta H et al (2014) T helper 17 cells play a critical pathogenic role in lung cancer. Proc Natl Acad Sci 111(15):5664\u20135669. https:\/\/doi.org\/10.1073\/pnas.1319051111","journal-title":"Proc Natl Acad Sci"},{"issue":"1","key":"5756_CR8","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.cmet.2017.10.006","volume":"27","author":"S Chatterjee","year":"2018","unstructured":"Chatterjee S, Daenthanasanmak A, Chakraborty P et al (2018) CD38-NAD + axis regulates immunotherapeutic anti-tumor T cell response. Cell Metab 27(1):85\u2013100","journal-title":"Cell Metab"},{"issue":"28","key":"5756_CR9","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.3748\/wjg.v28.i28.3573","volume":"28","author":"LG da Fonseca","year":"2022","unstructured":"da Fonseca LG, Araujo RLC (2022) Combination approaches in hepatocellular carcinoma: how systemic treatment can benefit candidates to locoregional modalities. World J Gastroenterol 28(28):3573\u20133585. https:\/\/doi.org\/10.3748\/wjg.v28.i28.3573","journal-title":"World J Gastroenterol"},{"issue":"2","key":"5756_CR10","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.ccr.2009.06.018","volume":"16","author":"DG DeNardo","year":"2009","unstructured":"DeNardo DG, Barreto JB, Andreu P et al (2009) CD4+ T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell 16(2):91\u2013102. https:\/\/doi.org\/10.1016\/j.ccr.2009.06.018","journal-title":"Cancer Cell"},{"issue":"4","key":"5756_CR11","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1158\/2159-8290.Cd-19-0297","volume":"10","author":"P Dey","year":"2020","unstructured":"Dey P, Li J, Zhang J et al (2020) Oncogenic KRAS-driven metabolic reprogramming in pancreatic cancer cells utilizes cytokines from the tumor microenvironment. Cancer Discov 10(4):608\u2013625. https:\/\/doi.org\/10.1158\/2159-8290.Cd-19-0297","journal-title":"Cancer Discov"},{"issue":"2","key":"5756_CR12","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.mam.2010.02.007","volume":"31","author":"M Frau","year":"2010","unstructured":"Frau M, Biasi F, Feo F, Pascale RM (2010) Prognostic markers and putative therapeutic targets for hepatocellular carcinoma. Mol Asp Med 31(2):179\u2013193. https:\/\/doi.org\/10.1016\/j.mam.2010.02.007","journal-title":"Mol Asp Med"},{"key":"5756_CR13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2215744120","author":"Z Gu","year":"2023","unstructured":"Gu Z, Wang L, Dong Q et al (2023) Aberrant LYZ expression in tumor cells serves as the potential biomarker and target for HCC and promotes tumor progression via csGRP78. Proc Natl Acad Sci. https:\/\/doi.org\/10.1073\/pnas.2215744120","journal-title":"Proc Natl Acad Sci"},{"issue":"3","key":"5756_CR14","doi-asserted-by":"publisher","first-page":"936","DOI":"10.7150\/jca.52439","volume":"12","author":"Y Han","year":"2021","unstructured":"Han Y, Wang J, Xu B (2021) Novel biomarkers and prediction model for the pathological complete response to neoadjuvant treatment of triple-negative breast cancer. J Cancer 12(3):936\u2013945. https:\/\/doi.org\/10.7150\/jca.52439","journal-title":"J Cancer"},{"key":"5756_CR15","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-7","author":"S H\u00e4nzelmann","year":"2013","unstructured":"H\u00e4nzelmann S, Castelo R, Guinney J (2013) GSVA: gene set variation analysis for microarray and RNA-Seq data. BMC Bioinform. https:\/\/doi.org\/10.1186\/1471-2105-14-7","journal-title":"BMC Bioinform"},{"key":"5756_CR16","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-021-08351-0","author":"L Hong","year":"2021","unstructured":"Hong L, Zhou Y, Xie X et al (2021) A stemness-based eleven-gene signature correlates with the clinical outcome of hepatocellular carcinoma. BMC Cancer. https:\/\/doi.org\/10.1186\/s12885-021-08351-0","journal-title":"BMC Cancer"},{"issue":"4","key":"5756_CR17","doi-asserted-by":"publisher","first-page":"3015","DOI":"10.3390\/curroncol28040264","volume":"28","author":"Z Hosseini-khah","year":"2021","unstructured":"Hosseini-khah Z, Babaei MR, Tehrani M et al (2021) SOX2 and Bcl-2 as a novel prognostic value in hepatocellular carcinoma progression. Curr Oncol 28(4):3015\u20133029. https:\/\/doi.org\/10.3390\/curroncol28040264","journal-title":"Curr Oncol"},{"issue":"3","key":"5756_CR18","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.jhep.2020.09.013","volume":"74","author":"J Howell","year":"2021","unstructured":"Howell J, Pedrana A, Schroeder SE et al (2021) A global investment framework for the elimination of hepatitis B. J Hepatol 74(3):535\u2013549. https:\/\/doi.org\/10.1016\/j.jhep.2020.09.013","journal-title":"J Hepatol"},{"key":"5756_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2020\/6784138","volume":"2020","author":"J-W Hu","year":"2020","unstructured":"Hu J-W, Ding G-Y, Fu P-Y et al (2020) Identification of FOS as a candidate risk gene for liver cancer by integrated bioinformatic analysis. Biomed Res Int 2020:1\u201310. https:\/\/doi.org\/10.1155\/2020\/6784138","journal-title":"Biomed Res Int"},{"key":"5756_CR20","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.bbrc.2022.07.047","volume":"623","author":"X Hu","year":"2022","unstructured":"Hu X, Pan H, Zhou S et al (2022) HS1BP3, transcriptionally regulated by ESR1, promotes hepatocellular carcinoma progression. Biochem Biophys Res Commun 623:111\u2013119. https:\/\/doi.org\/10.1016\/j.bbrc.2022.07.047","journal-title":"Biochem Biophys Res Commun"},{"issue":"1","key":"5756_CR21","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.ejso.2019.09.143","volume":"46","author":"S-H Jeong","year":"2020","unstructured":"Jeong S-H, Kim RB, Park SY et al (2020) Nomogram for predicting gastric cancer recurrence using biomarker gene expression. Eur J Surg Oncol 46(1):195\u2013201. https:\/\/doi.org\/10.1016\/j.ejso.2019.09.143","journal-title":"Eur J Surg Oncol"},{"issue":"10","key":"5756_CR22","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1038\/s41575-022-00620-y","volume":"19","author":"P Johnson","year":"2022","unstructured":"Johnson P, Zhou Q, Dao DY, Lo YMD et al (2022) Circulating biomarkers in the diagnosis and management of hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol 19(10):670\u2013681. https:\/\/doi.org\/10.1038\/s41575-022-00620-y","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"5756_CR23","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2020.573619","author":"Q Ju","year":"2020","unstructured":"Ju Q, Li X-M, Zhang H, Zhao Y-J (2020) BRCA1-associated protein is a potential prognostic biomarker and is correlated with immune infiltration in liver hepatocellular carcinoma: a pan-cancer analysis. Front Mol Biosci. https:\/\/doi.org\/10.3389\/fmolb.2020.573619","journal-title":"Front Mol Biosci"},{"issue":"1","key":"5756_CR24","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","volume":"28","author":"M Kanehisa","year":"2000","unstructured":"Kanehisa M (2000) KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res 28(1):27\u201330. https:\/\/doi.org\/10.1093\/nar\/28.1.27","journal-title":"Nucleic Acids Res"},{"key":"5756_CR25","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-022-02528-8","author":"V Karpisheh","year":"2022","unstructured":"Karpisheh V, Ahmadi M, Abbaszadeh-Goudarzi K et al (2022) The role of Th17 cells in the pathogenesis and treatment of breast cancer. Cancer Cell Int. https:\/\/doi.org\/10.1186\/s12935-022-02528-8","journal-title":"Cancer Cell Int"},{"key":"5756_CR26","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-1028-7","author":"B Li","year":"2016","unstructured":"Li B, Severson E, Pignon J-C et al (2016) Comprehensive analyses of tumor immunity: implications for cancer immunotherapy. Genome Biol. https:\/\/doi.org\/10.1186\/s13059-016-1028-7","journal-title":"Genome Biol"},{"issue":"21","key":"5756_CR27","doi-asserted-by":"publisher","first-page":"e108","DOI":"10.1158\/0008-5472.Can-17-0307","volume":"77","author":"T Li","year":"2017","unstructured":"Li T, Fan J, Wang B et al (2017) TIMER: a web server for comprehensive analysis of tumor-infiltrating immune cells. Can Res 77(21):e108\u2013e110. https:\/\/doi.org\/10.1158\/0008-5472.Can-17-0307","journal-title":"Can Res"},{"key":"5756_CR28","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.918140","author":"D Li","year":"2022","unstructured":"Li D, Li K, Zhang W et al (2022) The m6A\/m5C\/m1A regulated gene signature predicts the prognosis and correlates with the immune status of hepatocellular carcinoma. Front Immunol. https:\/\/doi.org\/10.3389\/fimmu.2022.918140","journal-title":"Front Immunol"},{"key":"5756_CR29","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.05038-22","author":"Z Liu","year":"2023","unstructured":"Liu Z, Zhang X, Zhang H et al (2023) Multi-omics analysis reveals intratumor microbes as immunomodulators in colorectal cancer. Microbiol Spectr. https:\/\/doi.org\/10.1128\/spectrum.05038-22","journal-title":"Microbiol Spectr"},{"issue":"12","key":"5756_CR30","doi-asserted-by":"publisher","first-page":"100260","DOI":"10.1016\/j.labinv.2023.100260","volume":"103","author":"Y-X Lou","year":"2023","unstructured":"Lou Y-X, Gu J, Zhu L et al (2023) TC2N promotes cell proliferation and metastasis in hepatocellular carcinoma by targeting the Wnt\/\u03b2-catenin signaling pathway. Lab Investig 103(12):100260","journal-title":"Lab Investig"},{"key":"5756_CR31","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ircmb.2019.07.008","author":"J Martinek","year":"2019","unstructured":"Martinek J, Wu TC, Cadena D et al (2019) Interplay between dendritic cells and cancer cells. Int Rev Cell Mol Biol. https:\/\/doi.org\/10.1016\/bs.ircmb.2019.07.008","journal-title":"Int Rev Cell Mol Biol"},{"issue":"5","key":"5756_CR32","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1016\/j.immuni.2009.09.014","volume":"31","author":"N Martin-Orozco","year":"2009","unstructured":"Martin-Orozco N, Muranski P, Chung Y et al (2009) T helper 17 cells promote cytotoxic T cell activation in tumor immunity. Immunity 31(5):787\u2013798. https:\/\/doi.org\/10.1016\/j.immuni.2009.09.014","journal-title":"Immunity"},{"issue":"1","key":"5756_CR33","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1093\/nar\/gkg034","volume":"31","author":"CV Mering","year":"2003","unstructured":"Mering CV, Huynen M, Jaeggi D et al (2003) STRING: a database of predicted functional associations between proteins. Nucleic Acids Res 31(1):258\u2013261. https:\/\/doi.org\/10.1093\/nar\/gkg034","journal-title":"Nucleic Acids Res"},{"issue":"4","key":"5756_CR34","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1016\/j.cell.2008.03.030","volume":"133","author":"A Murayama","year":"2008","unstructured":"Murayama A, Ohmori K, Fujimura A et al (2008) Epigenetic control of rDNA Loci in response to intracellular energy status. Cell 133(4):627\u2013639. https:\/\/doi.org\/10.1016\/j.cell.2008.03.030","journal-title":"Cell"},{"issue":"2","key":"5756_CR35","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1093\/nar\/gks1102","volume":"41","author":"C Peifer","year":"2013","unstructured":"Peifer C, Sharma S, Watzinger P et al (2013) Yeast Rrp8p, a novel methyltransferase responsible for m1A 645 base modification of 25S rRNA. Nucleic Acids Res 41(2):1151\u20131163. https:\/\/doi.org\/10.1093\/nar\/gks1102","journal-title":"Nucleic Acids Res"},{"key":"5756_CR36","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22875-w","author":"DH Peng","year":"2021","unstructured":"Peng DH, Rodriguez BL, Diao L et al (2021) Th17 cells contribute to combination MEK inhibitor and anti-PD-L1 therapy resistance in KRAS\/p53 mutant lung cancers. Nature Communications. https:\/\/doi.org\/10.1038\/s41467-021-22875-w","journal-title":"Nature Communications"},{"key":"5756_CR37","doi-asserted-by":"publisher","DOI":"10.23937\/2469-5696\/1410038","author":"Z Rahima","year":"2019","unstructured":"Rahima Z (2019) MEK1\/2 as a therapeutic target in sickle cell disease. Int J Blood Res Disord. https:\/\/doi.org\/10.23937\/2469-5696\/1410038","journal-title":"Int J Blood Res Disord"},{"issue":"7","key":"5756_CR38","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie ME, Phipson B, Wu D et al (2015) limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 43(7):e47\u2013e47. https:\/\/doi.org\/10.1093\/nar\/gkv007","journal-title":"Nucleic Acids Res"},{"key":"5756_CR39","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-77","author":"X Robin","year":"2011","unstructured":"Robin X, Turck N, Hainard A et al (2011) pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinform. https:\/\/doi.org\/10.1186\/1471-2105-12-77","journal-title":"BMC Bioinform"},{"issue":"1","key":"5756_CR40","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/s41423-020-00572-w","volume":"18","author":"B Ruf","year":"2020","unstructured":"Ruf B, Heinrich B, Greten TF (2020) Immunobiology and immunotherapy of HCC: spotlight on innate and innate-like immune cells. Cell Mol Immunol 18(1):112\u2013127. https:\/\/doi.org\/10.1038\/s41423-020-00572-w","journal-title":"Cell Mol Immunol"},{"issue":"43","key":"5756_CR41","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","volume":"102","author":"A Subramanian","year":"2005","unstructured":"Subramanian A, Tamayo P, Mootha VK et al (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci 102(43):15545\u201315550. https:\/\/doi.org\/10.1073\/pnas.0506580102","journal-title":"Proc Natl Acad Sci"},{"issue":"D1","key":"5756_CR42","doi-asserted-by":"publisher","first-page":"D607","DOI":"10.1093\/nar\/gky1131","volume":"47","author":"D Szklarczyk","year":"2019","unstructured":"Szklarczyk D, Gable AL, Lyon D et al (2019) STRING v11: protein\u2013protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res 47(D1):D607\u2013D613. https:\/\/doi.org\/10.1093\/nar\/gky1131","journal-title":"Nucleic Acids Res"},{"key":"5756_CR43","doi-asserted-by":"publisher","DOI":"10.3390\/ph12020070","author":"NK Tangudu","year":"2019","unstructured":"Tangudu NK, Buth N, Strnad P et al (2019) Deregulation of hepatic Mek1\/2\u2013Erk1\/2 signaling module in iron overload conditions. Pharmaceuticals. https:\/\/doi.org\/10.3390\/ph12020070","journal-title":"Pharmaceuticals"},{"key":"5756_CR44","doi-asserted-by":"publisher","DOI":"10.1080\/2162402x.2020.1784529","author":"X Tian","year":"2020","unstructured":"Tian X, Xu W, Wang Y et al (2020) Identification of tumor-infiltrating immune cells and prognostic validation of tumor-infiltrating mast cells in adrenocortical carcinoma: results from bioinformatics and real-world data. OncoImmunology. https:\/\/doi.org\/10.1080\/2162402x.2020.1784529","journal-title":"OncoImmunology"},{"issue":"15","key":"5756_CR45","doi-asserted-by":"publisher","first-page":"1450","DOI":"10.1056\/NEJMra1713263","volume":"380","author":"A Villanueva","year":"2019","unstructured":"Villanueva A, Longo DL (2019) Hepatocellular carcinoma. N Engl J Med 380(15):1450\u20131462. https:\/\/doi.org\/10.1056\/NEJMra1713263","journal-title":"N Engl J Med"},{"key":"5756_CR46","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.183723","author":"T Waku","year":"2016","unstructured":"Waku T, Nakajima Y, Yokoyama W et al (2016) NML-mediated rRNA base methylation links ribosomal subunit formation to cell proliferation in a p53-dependent manner. J Cell Sci. https:\/\/doi.org\/10.1242\/jcs.183723","journal-title":"J Cell Sci"},{"issue":"11","key":"5756_CR47","doi-asserted-by":"publisher","first-page":"3147","DOI":"10.1002\/1878-0261.13019","volume":"15","author":"L Wang","year":"2021","unstructured":"Wang L, Gao Y, Tong D et al (2021) MeCP2 drives hepatocellular carcinoma progression via enforcing HOXD3 promoter methylation and expression through the HB-EGF\/EGFR pathway. Mol Oncol 15(11):3147\u20133163. https:\/\/doi.org\/10.1002\/1878-0261.13019","journal-title":"Mol Oncol"},{"key":"5756_CR48","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2023.216240","author":"Y Xu","year":"2023","unstructured":"Xu Y, Zhang X, Zhang R et al (2023) AFP deletion leads to anti-tumorigenic but pro-metastatic roles in liver cancers with concomitant CTNNB1 mutations. Cancer Lett. https:\/\/doi.org\/10.1016\/j.canlet.2023.216240","journal-title":"Cancer Lett"},{"issue":"6","key":"5756_CR49","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1007\/s13402-021-00642-9","volume":"44","author":"W Xue","year":"2021","unstructured":"Xue W, Dong B, Zhao Y et al (2021) Upregulation of TTYH3 promotes epithelial-to-mesenchymal transition through Wnt\/\u03b2-catenin signaling and inhibits apoptosis in cholangiocarcinoma. Cell Oncol 44(6):1351\u20131361. https:\/\/doi.org\/10.1007\/s13402-021-00642-9","journal-title":"Cell Oncol"},{"issue":"22","key":"5756_CR50","doi-asserted-by":"publisher","first-page":"3613","DOI":"10.1080\/15384101.2015.1100777","volume":"14","author":"L Yang","year":"2015","unstructured":"Yang L, Song T, Chen L et al (2015) Nucleolar repression facilitates initiation and maintenance of senescence. Cell Cycle 14(22):3613\u20133623. https:\/\/doi.org\/10.1080\/15384101.2015.1100777","journal-title":"Cell Cycle"},{"issue":"5","key":"5756_CR51","doi-asserted-by":"publisher","first-page":"1793","DOI":"10.1053\/j.gastro.2020.07.047","volume":"159","author":"J-Y Yang","year":"2020","unstructured":"Yang J-Y, Jie Z, Mathews A et al (2020) Intestinal epithelial TBK1 prevents differentiation of T-helper 17 cells and tumorigenesis in mice. Gastroenterology 159(5):1793\u20131806. https:\/\/doi.org\/10.1053\/j.gastro.2020.07.047","journal-title":"Gastroenterology"},{"issue":"19","key":"5756_CR52","doi-asserted-by":"publisher","first-page":"3835","DOI":"10.1128\/mcb.00476-13","volume":"33","author":"L Yang","year":"2023","unstructured":"Yang L, Song T, Chen L et al (2023) Regulation of SirT1-nucleomethylin binding by rRNA coordinates ribosome biogenesis with nutrient availability. Mol Cell Biol 33(19):3835\u20133848. https:\/\/doi.org\/10.1128\/mcb.00476-13","journal-title":"Mol Cell Biol"},{"issue":"6","key":"5756_CR53","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1093\/jb\/mvy018","volume":"163","author":"W Yokoyama","year":"2018","unstructured":"Yokoyama W, Hirota K, Wan H et al (2018) rRNA adenine methylation requires T07A9.8 gene as rram-1 in Caenorhabditis elegans. J Biochem 163(6):465\u2013474. https:\/\/doi.org\/10.1093\/jb\/mvy018","journal-title":"J Biochem"},{"issue":"5","key":"5756_CR54","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","volume":"16","author":"G Yu","year":"2012","unstructured":"Yu G, Wang L-G, Han Y, He Q-Y (2012) clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS J Integr Biol 16(5):284\u2013287. https:\/\/doi.org\/10.1089\/omi.2011.0118","journal-title":"OMICS J Integr Biol"},{"key":"5756_CR55","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2020.104593","author":"R Zhang","year":"2021","unstructured":"Zhang R, Meng Z, Wu X et al (2021) Mortalin promotes breast cancer malignancy. Exp Mol Pathol. https:\/\/doi.org\/10.1016\/j.yexmp.2020.104593","journal-title":"Exp Mol Pathol"},{"issue":"2","key":"5756_CR56","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/j.intimp.2015.02.010","volume":"25","author":"P Zhao","year":"2015","unstructured":"Zhao P, Bu X, Wei X et al (2015) Dendritic cell immunotherapy combined with cytokine-induced killer cells promotes skewing toward Th2 cytokine profile in patients with metastatic non-small cell lung cancer. Int Immunopharmacol 25(2):450\u2013456. https:\/\/doi.org\/10.1016\/j.intimp.2015.02.010","journal-title":"Int Immunopharmacol"}],"container-title":["Journal of Cancer Research and Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-024-05756-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00432-024-05756-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-024-05756-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T03:22:59Z","timestamp":1717989779000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00432-024-05756-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,9]]},"references-count":56,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["5756"],"URL":"https:\/\/doi.org\/10.1007\/s00432-024-05756-9","relation":{},"ISSN":["1432-1335"],"issn-type":[{"type":"electronic","value":"1432-1335"}],"subject":[],"published":{"date-parts":[[2024,5,9]]},"assertion":[{"value":"17 February 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 April 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 May 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Ethical evaluation and permission were approved by the Ethics Committee of First Affiliated Hospital of Harbin Medical University. All donors provided written consent prior to participating in the research. The study adhered to the principles outlined in the Declaration of Helsinki.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"245"}}