Siglec-15 Silencing Inhibits Cell Proliferation and Promotes Cell Apoptosis by Inhibiting STAT1/STAT3 Signaling in Anaplastic Thyroid Carcinoma.

ABSTRACT: Thyroid cancer (THCA) represents a frequently seen endocrine cancer, which can be divided as anaplastic thyroid carcinoma (ATC), follicular thyroid carcinoma (FTC), and papillary thyroid carcinoma (PTC). A total of 362 IDEGs were obtained from TCGA-THCA and IMMPORT databases, which were found to be related to BP, CC, MF, and STAT signaling pathway upon GO functional annotation and KEGG analysis. This work identified 23 survival-related hub genes using WGCNA and uniCOX analysis. In addition, a risk prognosis model was constructed to obtain a signature involving fifteen IDEGs. According to survival and univariate along with multivariate analysis, high-risk patients had markedly dismal prognostic outcome compared with low-risk counterparts. Siglec-15 belongs to one of the fifteen IDEG signature, but the precise biological roles in diverse THCA subtypes are largely unclear. In this work, Siglec-15 expression evidently increased in ATC and FTC samples compared with matched surrounding PTC and THCA samples, which was used as a diagnostic biomarker for THCA. Siglec-15 RNAi significantly inhibited cell proliferation and promoted cell apoptosis. Meanwhile, Siglec-15 knockout suppressed the expression of STAT1, STAT3, and VEGF and promoted that of cleaved caspase-3. In vivo experiments revealed that transfection with vectors expressing STAT1 and STAT3 inhibited the Siglec-15 RNAi-induced inhibition on tumor growth and the increases in CD4⁺/CD8⁺ ratio. In conclusion, Siglec-15 expression increases in ATC and FTC, which promotes THCA occurrence via the STAT1/STAT3 signaling, in particular for FTC and ATC. Therefore, it is the possible marker that can be used to diagnose and treat THCA.

SUBMITTER: Hou X 

PROVIDER: S-EPMC9236774 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature