10.1016/s0029-7437(07)70168-4

Vollständiger Abstract

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Thyroid cancer (THCA) is the most common endocrine malignancy worldwide, understanding the pathophysiological mechanism is vital for developing effective strategies for prevention, diagnosis, and treatment. In this study, paired tumor and adjacent noncancerous tissues were collected from THCA patients. Cell viability and proliferation were assessed using CCK-8 and EdU assays. Cell migration and invasion were evaluated by wound healing and Transwell assays. Co-immunoprecipitation was performed to examine RNF123-mediated KAT5 ubiquitination, and chromatin immunoprecipitation was used to assess KAT5 enrichment at the PSPC1 promoter. An experimental lung metastasis model was established to evaluate the effects of RNF123 overexpression on tumor growth and pulmonary metastasis. RNF123 was down-regulated in THCA tissues and cell lines, and its overexpression suppressed cell viability, proliferation, migration, and invasion. KAT5 and PSPC1 were up-regulated in THCA cells. KAT5 knockdown inhibited THCA malignant behaviors. Mechanistically, RNF123 promoted the ubiquitination and degradation of KAT5, thereby reducing KAT5-mediated histone acetylation at the PSPC1 promoter and subsequent IGF1R up-regulation. In conclusion, RNF123 inhibited THCA malignant phenotype by promoting KAT5 ubiquitination and degradation, which reduced KAT5-mediated histone acetylation at the PSPC1 promoter, thereby down-regulating PSPC1 and IGF1R expressions.

Abstract: PubMed · Datensatz