{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T06:51:02Z","timestamp":1783147862991,"version":"3.54.6"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,12,4]],"date-time":"2022-12-04T00:00:00Z","timestamp":1670112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970523"],"award-info":[{"award-number":["81970523"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hepatic stellate cell (HSC) activation is a critical event in the development of hepatic fibrosis and hepatocellular carcinoma (HCC). By the release of soluble cytokines, chemokines, and chemotaxis, HSCs affect HCC cell phenotypes through a complex tumor microenvironment. In this study, weighted gene co\u2010expression network analysis (WGCNA) was used to identify the TGF\u2010\u03b2 signaling pathway as a key signaling pathway in Hep3B cells cultured in HSC conditioned medium. MIR4435\u20102HG is a hub lncRNA associated with the TGF\u2010\u03b2 signaling pathway and HSC activation. HSC\u2010condition medium (CM) culture induced HCC cell malignant behaviors, which were partially reversed by MIR4435\u20102HG silencing. miR\u2010506\u20103p directly bound to MIR4435\u20102HG and the 3\u2032UTR of TGFB1. Similarly, overexpression of miR\u2010506\u20103p also attenuated HSC\u2010CM\u2010induced malignant behavior of HCC cells. In HSC\u2010CM cultured HCC cells, the effects of MIR4435\u20102HG knockdown on TGFB1 expression and HCC cell phenotypes were partially reversed by miR\u2010506\u20103p inhibition. HSCs affected HCC cell phenotypes by releasing CXCL1. In an orthotopic xenotransplanted tumor model of HCC cells plus HSCs in mice, CXCR2 knockdown in HCC cells significantly inhibited tumorigenesis, which was partially reversed by MIR4435\u20102HG overexpression in HCC cells. In HCC tissue samples, the levels of CXCL1, TGF\u2010\u03b21, and MIR4435\u20102HG were upregulated, while miR\u2010506\u20103p expression was downregulated. In conclusion, HSC\u2010released CXCL1 aggravated HCC cell malignant behaviors through the MIR4435\u20102HG\/miR\u2010506\u20103p\/TGFB1 axis. In addition to CXCL1, the MIR4435\u20102HG\/miR\u2010506\u20103p\/TGFB1 axis might also be the underlying target for HCC therapy.<\/jats:p>","DOI":"10.1111\/cas.15605","type":"journal-article","created":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T10:24:21Z","timestamp":1664360661000},"page":"504-520","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Hepatic stellate cell\u2010released <scp>CXCL1<\/scp> aggravates <scp>HCC<\/scp> malignant behaviors through the <scp>MIR4435\u20102HG<\/scp>\/<scp>miR<\/scp>\u2010506\u20103p\/<scp>TGFB1<\/scp> axis"],"prefix":"10.1111","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4568-7198","authenticated-orcid":false,"given":"Shaling","family":"Li","sequence":"first","affiliation":[{"name":"Hunan Key Laboratory of Viral Hepatitis, Department of Infectious Disease, Xiangya Hospital Central South University  Changsha 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