Transcriptomics

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SETDB2 inhibits thyroid cancer progression by regulating the expression of the splicing factor U2AF1


ABSTRACT: Objective: This study aimed to investigate SETDB2 expression, clinical significance, and molecular mechanism in thyroid cancer progression. Methods: SETDB2 expression and prognosis were analyzed using TCGA and CPTAC databases, and validated by immunohistochemistry in 90 clinical samples (primary, recurrent, metastatic papillary, and anaplastic carcinoma). Overexpression and knockdown models were established in BCPAP and BHT101 cells. Proliferation was assessed by CCK‑8, colony formation, and EdU assays. RNA‑seq and qPCR identified downstream targets, with rescue experiments via U2AF1 overexpression. Results: SETDB2 was significantly downregulated in recurrent and metastatic papillary and anaplastic thyroid carcinoma, and low expression correlated with poor prognosis. SETDB2 overexpression suppressed proliferation and colony formation in anaplastic BHT101 cells, whereas knockdown promoted growth in papillary BCPAP cells. U2AF1 was identified as a key downstream target, and its overexpression partially reversed the inhibitory effects of SETDB2 on proliferation. Conclusion: SETDB2 acts as a tumor suppressor in thyroid cancer; its loss promotes progression, likely through regulating U2AF1. The SETDB2‑U2AF1 axis represents a potential therapeutic target.

ORGANISM(S): Homo sapiens

PROVIDER: GSE342848 | GEO | 2026/08/11

REPOSITORIES: GEO

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