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Functional assays evaluated the effects of C5AR1 knockdown on the malignant features of ATC cells. The interaction between C5AR1 and miR\u2010335\u20105p was confirmed using a luciferase reporter assay and Fluorescence in situ hybridization, and the impact of C5AR1 knockdown on the Toll\u2010like receptor (TLR) 1\/2 signaling pathway was examined. In vivo studies evaluated the effects of C5AR1 modulation on tumor growth and metastasis.\u00a0C5AR1 levels were elevated in ATC tumor samples and associated with poor survival in ATC patients. C5AR1 knockdown impeded ATC cell proliferation, migration, and invasion in vitro. MiR\u2010335\u20105p was identified as an upstream regulator of C5AR1, which negatively modulates C5AR1 expression. C5AR1 knockdown diminished TLR1, TLR2, and myeloid differentiation primary response 88 (MyD88) levels, while C5AR1 overexpression activated this pathway. Blocking TLR1\/2 signaling abrogated the oncogenic effects of C5AR1 overexpression. C5AR1 silencing inhibited tumor growth and lung metastasis of ATC cells in nude mice.\u00a0C5AR1 contributes to ATC tumorigenesis and metastasis by activating the TLR1\/2 pathway, and is negatively regulated by miR\u2010335\u20105p. Targeting the miR\u2010335\u20105p\/C5AR1\/TLR1\/2 axis represents a potential therapeutic strategy for ATC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mc.23784","type":"journal-article","created":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T15:38:01Z","timestamp":1719502681000},"page":"1938-1952","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["C5AR1\u2010induced TLR1\/2 pathway activation drives proliferation and metastasis in anaplastic thyroid cancer"],"prefix":"10.1002","volume":"63","author":[{"given":"Bo","family":"Liu","sequence":"first","affiliation":[{"name":"Department of General Surgery The First Hospital of Hebei Medical University Shijiazhuang Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueyao","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of General Surgery The First Hospital of Hebei Medical University Shijiazhuang Hebei 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