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PCR and fluorescence in situ hybridization were used to explore the expression features of circLDLRAD3 in OSCC. The effects of circLDLRAD3 on the behaviour of OSCC were investigated using CCK\u20108, colony formation assay, transwell and animal experiments. Bioinformatics analysis along with dual luciferase reporter assay and RIP assay were used to reveal the interaction between circLDLRAD3, miR\u2010558 and Smad4. It was revealed that circLDLRAD3 exhibited low expression status in OSCC. CircLDLRAD3 inhibits proliferation, migration, and invasion of OSCC cells both in vitro and in vivo. Mechanistically, circLDLRAD3 could bind with miR\u2010558 to positively regulate its target gene Smad4 expression. Rescue experiments further confirmed both miR\u2010558 overexpression and Smad4 knockdown could reverse the influence of circLDLRAD3 on OSCC phenotypes. Moreover, circLDLRAD3 regulate the TGF\u2010\u03b2 signalling pathways to influence EMT through miR\u2010558\/Smad4 axis. Our study found that circLDLRAD3 is downregulated in OSCC and verified its tumour suppressor function and mechanism in OSCC through sponging miR\u2010558 to regulate miR\u2010558\/Smad4\/TGF\u2010\u03b2 axis. The characterization of such regulating network uncovers an important mechanism underlying OSCC progression, which could provide promising targets targeted therapy strategies for OSCC in the future.<\/jats:p>","DOI":"10.1111\/jcmm.17898","type":"journal-article","created":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T05:57:58Z","timestamp":1691733478000},"page":"3271-3285","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>CircLDLRAD3<\/scp> inhibits Oral squamous cell carcinoma progression by regulating <scp>miR<\/scp>\u2010558\/Smad4\/<scp>TGF<\/scp>\u2010\u03b2"],"prefix":"10.1111","volume":"27","author":[{"given":"Xue","family":"Zhang","sequence":"first","affiliation":[{"name":"The VIP Department School and Hospital of Stomatology, China Medical University  Shenyang China"},{"name":"Department of Surgical Oncology and General Surgery The First Hospital of China Medical University; Key Laboratory of 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