{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:13:43Z","timestamp":1790972023004,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,9,29]],"date-time":"2024-09-29T00:00:00Z","timestamp":1727568000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2024,9,29]],"date-time":"2024-09-29T00:00:00Z","timestamp":1727568000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2304800"],"award-info":[{"award-number":["2022YFC2304800"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Epithelial\u2010mesenchymal transition (EMT) is central to HCC metastasis, in which RNA\u2010binding proteins (RBPs) play a key role.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To explore the role of RBPs in metastasis of hepatocellular carcinoma (HCC), whole transcriptome sequencing was conducted to identify differential RBPs between HCC with metastasis and HCC without metastasis. The influence of RBPs on metastasis of HCC was verified by\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      experiments. The interaction of RBPs with non\u2010coding RNAs was evaluated by RNA immunoprecipitation and pull\u2010down assays. RNA sequencing, whole\u2010genome sequencing, and alternative splicing analysis were further performed to clarify post\u2010transcriptional regulation mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Whole transcriptome sequencing results showed that expression of thioredoxin (Trx) was significantly upregulated in HCC patients with metastasis. Trx was also found to be associated with poor prognosis in HCC patients. Overexpression of Trx could promote migration and invasion of HCC cells\n                      <jats:italic>in vitro<\/jats:italic>\n                      and increase the rate of lung metastasis of HCC cells\n                      <jats:italic>in vivo<\/jats:italic>\n                      . Moreover, binding assays showed that Trx could bind to LINC00152. As a result, LINC00152 was verified to determine the pro\u2010metastasis function of Trx by knockdown assay. Furthermore, we revealed that Trx could regulate metastasis\u2010associated alternative splicing program. Specifically, angiopoietin 1 (ANGPT1) was the splicing target; the splicing isoform switching of ANGPT1 could activate the PI3K\u2013Akt pathway, upregulate EMT\u2010associated proteins, and promote migration and invasion of HCC cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We found that Trx could interact with LINC00152 and promote HCC metastasis via regulating alternative splicing, indicating that Trx may serve as a novel therapeutic target for HCC treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jgh.16735","type":"journal-article","created":{"date-parts":[[2024,9,29]],"date-time":"2024-09-29T20:24:18Z","timestamp":1727641458000},"page":"2892-2902","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["RNA\u2010binding protein Trx regulates alternative splicing and promotes metastasis of HCC via interacting with LINC00152"],"prefix":"10.1111","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2581-1048","authenticated-orcid":false,"given":"Xiangnan","family":"Teng","sequence":"first","affiliation":[{"name":"Center of Infectious Diseases West China Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0556-8722","authenticated-orcid":false,"given":"Jin","family":"Shang","sequence":"additional","affiliation":[{"name":"Center of Infectious Diseases West China Hospital, Sichuan University  Chengdu China"},{"name":"Liver Transplantation Center and HBP Surgery, Sichuan Clinical Research Center for Cancer Sichuan Cancer Hospital &amp; Institute, Sichuan Cancer Center Affiliated Cancer Hospital of University of Electronic Science and Technology of China  Chengdu 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