To investigate the expression of SF3B5 in papillary thyroid carcinoma (PTC) and its correlation with clinicopathological characteristics of PTC patients, and to reveal the function and molecular mechanisms of SF3B5 in PTC progression.

The expression levels of SF3B5 in PTC and normal tissues from the The Cancer Genome Atlas (TCGA) database were analyzed for their correlation with clinicopathological features and prognosis. A retrospective study was conducted on 95 patients with PTC selected by simple random sampling from January 2011 to June 2015. Clinicopathological data were collected, and SF3B5 expression in PTC tissues was detected by immunohistochemical staining. The Chi-square test, univariate, and multivariate Logistic regression analyses were used to explore the correlation between SF3B5 and PTC clinicopathological characteristics. TPC-1 and KTC-1 cell lines with overexpressing SF3B5 were constructed for cell phenotype experiments to investigate the effects of SF3B5 on cell proliferation and migration. Total RNA was extracted for transcriptome sequencing. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) enrichment analyses were performed on the transcriptome sequencing data and TCGA database data. Downstream pathway molecules were validated by Western blotting.

(1) TCGA database analysis showed that SF3B5 expression was lower in PTC tissues compared to adjacent normal tissues. SF3B5 expression was significantly decreased in PTC tissues with BRAF mutation, extrathyroidal extension, lateral lymph node metastasis (LLNM), T3/T4 stage, and R1/R2 resection status (P<0.05). (2) Immunohistochemical staining analysis revealed low SF3B5 expression in 50 cases and high expression in 45 cases among PTC tissues. Compared to patients with high SF3B5 expression, the proportion of patients with LLNM was significantly higher in the low SF3B5 expression group (P=0.043). (3) Low SF3B5 expression and extrathyroidal extension were independent risk factors affecting LLNM in PTC patients. (4) SF3B5 inhibited PTC progression through the JAK-STAT and TGF-β signaling pathways.

SF3B5 is downregulated in PTC, and its low expression serves as an independent risk factor for lateral lymph node metastasis in PTC patients. Mechanistically, SF3B5 suppresses tumor progression through negative regulation of the JAK-STAT and TGF-β signaling pathways. These findings suggest that SF3B5 may serve as a novel biomarker for assessing metastatic risk and represent a potential therapeutic target in PTC.