Abstract
BACKGROUND: Papillary thyroid carcinoma (PTC) is the most commonly diagnosed subtype of thyroid cancer and represents a highly prevalent form of endocrine malignancy. AIMS: This study aimed to investigate the role and molecular mechanism of CHI3L1 in PTC progression. METHODS AND RESULTS: CHI3L1 expression in PTC was analyzed using public datasets. Cell proliferation was assessed using the CCK‐8 assay and colony formation assay. Tumor growth was evaluated using nude mouse xenograft models. Cell invasion was evaluated using the transwell assay, while cell migration was assessed with the wound healing assay. Transcriptomic analysis was conducted to examine the molecular mechanism, and real‐time quantitative PCR was performed for gene expression validation. The findings revealed that CHI3L1 expression was upregulated in various cancers, mainly in PTC. Both in vitro and in vivo assays demonstrated that cell proliferation was suppressed when CHI3L1 was knocked down. Transcriptome sequencing indicated that CHI3L1 knockdown was associated with migration‐related pathways and the TP53 signaling pathway. Transwell assays showed reduced cell invasion upon CHI3L1 suppression, while wound healing assays demonstrated decreased cell migration. Following CHI3L1 silencing, real‐time quantitative PCR verified the overexpression of TP53‐related genes. Survival analysis further indicated a correlation between elevated CHI3L1 expression and reduced survival rates. CONCLUSION: This study identified that CHI3L1 was an oncogene in PTC and promotes tumor cell proliferation associated with downregulating the TP53 pathway. It provides new evidence supporting CHI3L1 as a potential molecular target for future therapeutic investigation in PTC.