{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T05:55:44Z","timestamp":1790920544802,"version":"4.1.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017700","name":"Henan Provincial Science and Technology Research Project","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014717","name":"Youth Science Fund Project","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014717","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Circular RNA (circRNA) has been shown to have a pivotal role in the initiation and evolution of multiple tumors, but its function in hepatocellular carcinoma (HCC) requires further elucidation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      circUGP2 (hsa_circ_0001020) was identified in the GEO database by HCC circRNA microarray. Subsequently, an assessment was conducted to determine the biological effects of circUGP2, employing a series of analytical methods, including CCK8, EdU, colony formation, transwell, scratch assays, and\n                      <jats:italic>in vivo<\/jats:italic>\n                      experimentation. To explore the functions of circUGP2 as a sponge, including RNA pull-down, microRNA-seq, fluorescence\n                      <jats:italic>in situ<\/jats:italic>\n                      hybridization (FISH), RNA immunoprecipitation (RIP), and luciferase reporter assays were employed. Mass spectrometry (MS), RIP, and co-inmunoprecipitation (Co-IP) were employed to examine the interaction between cirrcUGP2 and up-frameshift protein 1 (UPF1).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      circUGP2 was downregulated in HCC tissues and cells, which inhibited the growth and spread of HCC\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      . In the mechanisms, circUGP2 has the capacity to modulate KLF4 by sponging miR-137-3p, thereby suppressing HCC growth and migration. In addition, circUGP2 could combine with UPF1 and facilitate an interplay between UPF1 and AKT, influencing tumor progression in HCC via inactivation of the PI3K\/AKT signaling pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>circUGP2 has a crucial function in HCC development by modulating the miR-137-3p\/KLF4 axis to inactivate the PI3K\/AKT\/mTOR pathway and by interacting with UPF1. The findings indicate the potential of circUGP2 as a novel biomarker and target for HCC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1926747","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T05:37:29Z","timestamp":1790919449000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["CircUGP2 inhibits tumor progression via PI3K\/AKT\/mTOR signaling through sponging miR-137-3p and interacting with UPF1 in hepatocellular carcinoma"],"prefix":"10.3389","volume":"17","author":[{"given":"Longfei","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, China"]},{"name":"Key Laboratory of Precision Diagnosis and Treatment in General Surgical (Hepatobiliary and Pancreatic) Diseases of Health Commission of Henan Province","place":["Zhengzhou, 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