{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:16:02Z","timestamp":1790694962325,"version":"4.1.0"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T00:00:00Z","timestamp":1709510400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T00:00:00Z","timestamp":1709510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007194","name":"Wenzhou Municipal Science and Technology Bureau","doi-asserted-by":"publisher","award":["Y20220023"],"award-info":[{"award-number":["Y20220023"]}],"id":[{"id":"10.13039\/501100007194","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Long noncoding RNA small nucleolar RNA host gene 5 (SNHG5) is an oncogene found in various human cancers. However, it is unclear what role SNHG5 plays in activating hepatic stellate cells (HSCs) and liver fibrosis. In this study, SNHG5 was found to be upregulated in activated HSCs in vitro and in primary HSCs isolated from fibrotic liver in vivo, and inhibition of SNHG5 suppressed HSC activation. Notably, Neurofibromin 2 (NF2), the main activator for Hippo signalling, was involved in the effects of SNHG5 on HSC activation. The interaction between SNHG5 and NF2 protein was further confirmed, and preventing the combination of the two could effectively block the effects of SNHG5 inhibition on EMT process and Hippo signaling. Additionally, higher SNHG5 was found in chronic hepatitis B patients and associated with the fibrosis stage. Altogether, we demonstrate that SNHG5 could serve\u00a0as an activated HSCs regulator via regulating NF2 and Hippo pathway.<\/jats:p>","DOI":"10.1038\/s42003-024-05971-7","type":"journal-article","created":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T11:02:14Z","timestamp":1709550134000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["LncRNA-SNHG5 mediates activation of hepatic stellate cells by regulating NF2 and Hippo pathway"],"prefix":"10.1038","volume":"7","author":[{"given":"Rongrong","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yating","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhichao","family":"Lang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weizhi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8770-4219","authenticated-orcid":false,"given":"Jianjian","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,4]]},"reference":[{"key":"5971_CR1","doi-asserted-by":"publisher","first-page":"2095","DOI":"10.1016\/S0140-6736(12)61728-0","volume":"380","author":"R Lozano","year":"2012","unstructured":"Lozano, R. et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the global burden of disease Study 2010. Lancet 380, 2095\u20132128 (2012).","journal-title":"Lancet"},{"key":"5971_CR2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.603649","volume":"12","author":"S Mountford","year":"2021","unstructured":"Mountford, S. et al. Modulation of liver inflammation and fibrosis by interleukin-37. Front. Immunol. 12, 603649 (2021).","journal-title":"Front. Immunol."},{"key":"5971_CR3","doi-asserted-by":"publisher","first-page":"14","DOI":"10.5152\/tjg.2018.17330","volume":"29","author":"MM Aydin","year":"2018","unstructured":"Aydin, M. M. & Akcali, K. C. Liver fibrosis. Turk J. Gastroenterol. 29, 14\u201321 (2018).","journal-title":"Turk J. Gastroenterol."},{"key":"5971_CR4","doi-asserted-by":"crossref","unstructured":"Munakarmi, S. et al. Hepatoprotective effects of a natural flavanol 3,3\u2019-Diindolylmethane against CCl(4)-induced chronic liver injury in mice and TGF\u03b21-induced EMT in mouse hepatocytes via activation of Nrf2 cascade. Int. J. Mol. Sci. 23, 11407 (2022).","DOI":"10.3390\/ijms231911407"},{"key":"5971_CR5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.968879","volume":"13","author":"CC Gao","year":"2022","unstructured":"Gao, C. C., Bai, J., Han, H. & Qin, H. Y. The versatility of macrophage heterogeneity in liver fibrosis. Front. Immunol. 13, 968879 (2022).","journal-title":"Front. Immunol."},{"key":"5971_CR6","doi-asserted-by":"crossref","unstructured":"Wei, M. et al. Hepatocyte-specific Smad4 deficiency alleviates liver fibrosis via the p38\/p65 pathway. Int. J. Mol. Sci. 23, 11696 (2022).","DOI":"10.3390\/ijms231911696"},{"key":"5971_CR7","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1038\/s41575-020-00372-7","volume":"18","author":"T Kisseleva","year":"2021","unstructured":"Kisseleva, T. & Brenner, D. Molecular and cellular mechanisms of liver fibrosis and its regression. Nat. Rev. Gastroenterol. Hepatol. 18, 151\u2013166 (2021).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"5971_CR8","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0752-1","volume":"9","author":"L Ma","year":"2018","unstructured":"Ma, L. et al. MicroRNA-214 promotes hepatic stellate cell activation and liver fibrosis by suppressing sufu expression. Cell Death Dis. 9, 718 (2018).","journal-title":"Cell Death Dis."},{"key":"5971_CR9","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.devcel.2019.06.003","volume":"50","author":"Y Zheng","year":"2019","unstructured":"Zheng, Y. & Pan, D. The hippo signaling pathway in development and disease. Dev. Cell 50, 264\u2013282 (2019).","journal-title":"Dev. Cell"},{"key":"5971_CR10","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1016\/j.cell.2015.10.044","volume":"163","author":"FX Yu","year":"2015","unstructured":"Yu, F. X., Zhao, B. & Guan, K. L. Hippo pathway in organ size control, tissue homeostasis and cancer. Cell 163, 811\u2013828 (2015).","journal-title":"Cell"},{"key":"5971_CR11","doi-asserted-by":"crossref","unstructured":"Fujisawa, K. et al. Metabolic alterations in spheroid-cultured hepatic stellate cells. Int. J. Mol. Sci. 21, 3451 (2020).","DOI":"10.3390\/ijms21103451"},{"key":"5971_CR12","first-page":"37","volume":"31","author":"Y Wang","year":"2021","unstructured":"Wang, Y., Yu, H. & He, J. Involvement of the hippo pathway in the development of diabetes. Discov. Med. 31, 37\u201344 (2021).","journal-title":"Discov. Med."},{"key":"5971_CR13","doi-asserted-by":"crossref","unstructured":"Liu, X., Chen, X., Liu, L., Xia, J. & Zhang, H. AKAP12 inhibits the proliferation of ovarian cancer by activating the Hippo pathway. Oncologie 26, 105\u2013116 (2023).","DOI":"10.1515\/oncologie-2023-0242"},{"key":"5971_CR14","doi-asserted-by":"crossref","unstructured":"Porazinski, S. & Ladomery, M. Alternative splicing in the hippo pathway-implications for disease and potential therapeutic targets. Genes (Basel) 9, 161 (2018).","DOI":"10.3390\/genes9030161"},{"key":"5971_CR15","doi-asserted-by":"crossref","unstructured":"Allegra, A., Pioggia, G., Innao, V., Musolino, C. & Gangemi, S. New insights into YES-associated protein signaling pathways in hematological malignancies: diagnostic and therapeutic challenges. Cancers 13, 1981 (2021).","DOI":"10.3390\/cancers13081981"},{"key":"5971_CR16","doi-asserted-by":"publisher","first-page":"323","DOI":"10.3389\/fimmu.2020.00323","volume":"11","author":"S Wang","year":"2020","unstructured":"Wang, S. et al. The cosstalk between hippo-YAP pathway and innate immunity. Front. Immunol. 11, 323 (2020).","journal-title":"Front. Immunol."},{"key":"5971_CR17","doi-asserted-by":"crossref","unstructured":"Hicks-Berthet, J. & Varelas, X. Integrin-FAK-CDC42-PP1A signaling gnaws at YAP\/TAZ activity to control incisor stem cells. Bioessays. 39, 1700116 (2017).","DOI":"10.1002\/bies.201700116"},{"key":"5971_CR18","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/3399357","volume":"2021","author":"C Li","year":"2021","unstructured":"Li, C., Zhang, R., Zhan, Y. & Zheng, J. Resveratrol inhibits hepatic stellate cell activation via the hippo pathway. Mediators Inflamm. 2021, 3399357 (2021).","journal-title":"Mediators Inflamm."},{"key":"5971_CR19","doi-asserted-by":"crossref","unstructured":"Bridges, M. C., Daulagala, A. C. & Kourtidis, A. LNCcation: lncRNA localization and function. J. Cell Biol. 220, e202009045 (2021).","DOI":"10.1083\/jcb.202009045"},{"key":"5971_CR20","doi-asserted-by":"crossref","unstructured":"Dmochowska, N. et al. 89Zr-pro-MMP-9 F(ab\u2019)2 detects colitis induced intestinal and kidney fibrosis. Sci. Rep. 10, 20372 (2020).","DOI":"10.1038\/s41598-020-77390-7"},{"key":"5971_CR21","doi-asserted-by":"publisher","first-page":"2491","DOI":"10.1007\/s00018-016-2174-5","volume":"73","author":"SU Schmitz","year":"2016","unstructured":"Schmitz, S. U., Grote, P. & Herrmann, B. G. Mechanisms of long noncoding RNA function in development and disease. Cell Mol. Life Sci. 73, 2491\u20132509 (2016).","journal-title":"Cell Mol. Life Sci."},{"key":"5971_CR22","first-page":"143","volume":"33","author":"S Huo","year":"2022","unstructured":"Huo, S., Liu, L., Li, Q. & Wang, J. Modulation of myeloid-derived suppressor cells by long non-coding RNAs in the tumor microenvironment and tumorigenesis. Discov. Med. 33, 143\u2013151 (2022).","journal-title":"Discov. Med."},{"key":"5971_CR23","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.canlet.2018.01.001","volume":"41.8","author":"H Lv","year":"2018","unstructured":"Lv, H., Lv, G., Han, Q., Yang, W. & Wang, H. Noncoding RNAs in liver cancer stem cells: the big impact of little things. Cancer Lett. 41.8, 51\u201363 (2018).","journal-title":"Cancer Lett."},{"key":"5971_CR24","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2019.194419","volume":"1863","author":"EK Robinson","year":"2020","unstructured":"Robinson, E. K., Covarrubias, S. & Carpenter, S. The how and why of lncRNA function: an innate immune perspective. Biochim. Biophys. Acta. Gene. Regul. Mech. 1863, 194419 (2020).","journal-title":"Biochim. Biophys. Acta. Gene. Regul. Mech."},{"key":"5971_CR25","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1007\/s00109-017-1586-5","volume":"95","author":"F Yu","year":"2017","unstructured":"Yu, F., Jiang, Z., Chen, B., Dong, P. & Zheng, J. NEAT1 accelerates the progression of liver fibrosis via regulation of microRNA-122 and Kruppel-like factor 6. J. Mol. Med. 95, 1191\u20131202 (2017).","journal-title":"J. Mol. Med."},{"key":"5971_CR26","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00204-4","volume":"8","author":"K Zhang","year":"2017","unstructured":"Zhang, K. et al. The liver-enriched lnc-LFAR1 promotes liver fibrosis by activating TGF\u03b2 and Notch pathways. Nat. Commun. 8, 144 (2017).","journal-title":"Nat. Commun."},{"key":"5971_CR27","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.ymthe.2016.10.015","volume":"25","author":"F Yu","year":"2017","unstructured":"Yu, F., Chen, B., Dong, P. & Zheng, J. HOTAIR epigenetically modulates PTEN expression via MicroRNA-29b: a novel mechanism in regulation of liver fibrosis. Mol. Ther. 25, 205\u2013217 (2017).","journal-title":"Mol. Ther."},{"key":"5971_CR28","doi-asserted-by":"crossref","unstructured":"Li, X. et al. Long non-coding RNA SNHG5 promotes glioma progression via miR-205\/E2F3 axis. Biosci. Rep. 39, BSR20190668 (2019).","DOI":"10.1042\/BSR20190668"},{"key":"5971_CR29","first-page":"3592","volume":"24","author":"PA Hu","year":"2020","unstructured":"Hu, P. A., Miao, Y. Y., Yu, S. & Guo, N. Long non-coding RNA SNHG5 promotes human hepatocellular carcinoma progression by regulating miR-363-3p\/RNF38 axis. Eur. Rev. Med. Pharmacol. Sci. 24, 3592\u20133604 (2020).","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"5971_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0882-5","volume":"9","author":"Y Li","year":"2018","unstructured":"Li, Y. et al. Long non-coding RNA SNHG5 promotes human hepatocellular carcinoma progression by regulating miR-26a-5p\/GSK3beta signal pathway. Cell Death Dis. 9, 888 (2018).","journal-title":"Cell Death Dis."},{"key":"5971_CR31","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1080\/15384047.2018.1537579","volume":"20","author":"M Zhang","year":"2019","unstructured":"Zhang, M. et al. LncRNA SNHG5 affects cell proliferation, metastasis and migration of colorectal cancer through regulating miR-132-3p\/CREB5. Cancer Biol. Ther. 20, 524\u2013536 (2019).","journal-title":"Cancer Biol. Ther."},{"key":"5971_CR32","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1186\/s13287-020-01990-3","volume":"11","author":"L Liu","year":"2020","unstructured":"Liu, L. et al. si-SNHG5-FOXF2 inhibits TGF-beta1-induced fibrosis in human primary endometrial stromal cells by the Wnt\/beta-catenin signalling pathway. Stem. Cell Res. Ther. 11, 479 (2020).","journal-title":"Stem. Cell Res. Ther."},{"key":"5971_CR33","doi-asserted-by":"publisher","first-page":"G1093","DOI":"10.1152\/ajpgi.00292.2009","volume":"297","author":"SS Choi","year":"2009","unstructured":"Choi, S. S. et al. Hedgehog pathway activation and epithelial-to-mesenchymal transitions during myofibroblastic transformation of rat hepatic cells in culture and cirrhosis. Am. J. Physiol. Gastrointest. Liver Physiol. 297, G1093\u2013G1106 (2009).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"5971_CR34","doi-asserted-by":"publisher","first-page":"14751","DOI":"10.1073\/pnas.95.25.14751","volume":"95","author":"V Ribon","year":"1998","unstructured":"Ribon, V., Johnson, J. H., Camp, H. S. & Saltiel, A. R. Thiazolidinediones and insulin resistance: peroxisome proliferatoractivated receptor gamma activation stimulates expression of the CAP gene. Proc. Natl Acad. Sci. USA 95, 14751\u201314756 (1998).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"5971_CR35","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-1068-x","volume":"9","author":"F Yu","year":"2018","unstructured":"Yu, F., Geng, W., Dong, P., Huang, Z. & Zheng, J. LncRNA-MEG3 inhibits activation of hepatic stellate cells through SMO protein and miR-212. Cell Death Dis. 9, 1014 (2018).","journal-title":"Cell Death Dis."},{"key":"5971_CR36","doi-asserted-by":"crossref","unstructured":"Li, Y. et al. LncRNA SNHG5 promotes the proliferation and cancer stem cell-like properties of HCC by regulating UPF1 and Wnt-signaling pathway. Cancer Gene Ther. 29, 1373\u20131383 (2022).","DOI":"10.1038\/s41417-022-00456-3"},{"key":"5971_CR37","doi-asserted-by":"crossref","unstructured":"Masliantsev, K., Karayan-Tapon, L. & Guichet, P. O. Hippo signaling pathway in gliomas. Cells 10, 184 (2021).","DOI":"10.3390\/cells10010184"},{"key":"5971_CR38","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1038\/nmeth.1611","volume":"8","author":"M Bellucci","year":"2011","unstructured":"Bellucci, M., Agostini, F., Masin, M. & Tartaglia, G. G. Predicting protein associations with long noncoding RNAs. Nat. Methods 8, 444\u2013445 (2011).","journal-title":"Nat. Methods"},{"key":"5971_CR39","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-04728-6","volume":"13","author":"Y Qin","year":"2022","unstructured":"Qin, Y. et al. RBM47\/SNHG5\/FOXO3 axis activates autophagy and inhibits cell proliferation in papillary thyroid carcinoma. Cell Death Dis. 13, 270 (2022).","journal-title":"Cell Death Dis."},{"key":"5971_CR40","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2018.12.003","volume":"62","author":"EH Lee","year":"2019","unstructured":"Lee, E. H. et al. Liquiritigenin inhibits hepatic fibrogenesis and TGF-beta1\/Smad with Hippo\/YAP signal. Phytomedicine 62, 152780 (2019).","journal-title":"Phytomedicine"},{"key":"5971_CR41","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.1053\/j.gastro.2017.12.022","volume":"154","author":"K Du","year":"2018","unstructured":"Du, K. et al. Hedgehog-YAP Signaling pathway regulates glutaminolysis to control activation of hepatic stellate cells. Gastroenterology 154, 1465\u20131479.e1413 (2018).","journal-title":"Gastroenterology"},{"key":"5971_CR42","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2022.154466","volume":"107","author":"T Yang","year":"2022","unstructured":"Yang, T. et al. TKF, a mexicanolide-type limonoid derivative, suppressed hepatic stellate cells activation and liver fibrosis through inhibition of the YAP\/Notch3 pathway. Phytomedicine 107, 154466 (2022).","journal-title":"Phytomedicine"},{"key":"5971_CR43","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1038\/s42003-023-04670-z","volume":"6","author":"Y Zhan","year":"2023","unstructured":"Zhan, Y. et al. LncRNA-MIAT activates hepatic stellate cells via regulating Hippo pathway and epithelial-to-mesenchymal transition. Commun. Biol. 6, 285 (2023).","journal-title":"Commun. Biol."},{"key":"5971_CR44","doi-asserted-by":"publisher","first-page":"23337","DOI":"10.1074\/jbc.M700194200","volume":"282","author":"M Zeisberg","year":"2007","unstructured":"Zeisberg, M. et al. Fibroblasts derive from hepatocytes in liver fibrosis via epithelial to mesenchymal transition. J. Biol. Chem. 282, 23337\u201323347 (2007).","journal-title":"J. Biol. Chem."},{"key":"5971_CR45","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1093\/abbs\/gmt143","volume":"46","author":"W Chang","year":"2014","unstructured":"Chang, W. et al. Isolation and culture of hepatic stellate cells from mouse liver. Acta Biochim. Biophys. Sin. 46, 291\u2013298 (2014).","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"5971_CR46","doi-asserted-by":"publisher","first-page":"1566","DOI":"10.1007\/s11064-020-03021-2","volume":"45","author":"M Chen","year":"2020","unstructured":"Chen, M. et al. Long noncoding RNA SNHG5 knockdown alleviates neuropathic pain by targeting the miR-154-5p\/CXCL13 axis. Neurochem. Res. 45, 1566\u20131575 (2020).","journal-title":"Neurochem. Res."}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-024-05971-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-024-05971-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-024-05971-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T16:47:35Z","timestamp":1709916455000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-024-05971-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,4]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["5971"],"URL":"https:\/\/doi.org\/10.1038\/s42003-024-05971-7","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,4]]},"assertion":[{"value":"19 April 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 February 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 March 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"266"}}