BRD9 promotes the malignant phenotype of thyroid cancer by activating the MAPK/ERK pathway.

Abstract

Thyroid cancer is one of the most common endocrine gland malignancies in China. During gene transcription, the bromodomain and extraterminal domain (BET) proteins perform epigenome interpretation tasks. Bromodomain-containing protein 9 (BRD9) is one of the BET family members. Increasing evidence has implicated that BRD9 plays significant roles in multiple malignancies. However, its role in thyroid cancer is still not fully understood. In this research, our results demonstrated that high expression of BRD9 can facilitate the malignant phenotype of thyroid cancer cell lines, while low expression of BRD9 can impede the malignant phenotype of thyroid cancer cell lines. Pharmacologically, I-BRD9 treatment inhibits the proliferation and promotes the rate of apoptosis in thyroid cancer cell lines. Moreover, our results also revealed that BRD9 promoted xenograft tumor growth. In addition, our study showed that the expression of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase (ERK) pathway-related proteins was decreased in BRD9 knockdown thyroid cancer cells, such as Raf, ERK, p-ERK, c-Fos, and c-Myc, which could be significantly reversed by overexpressing the BRD9 in different thyroid cancer cells. After the specific inhibitor of ERK (SCH772984) was applied to thyroid cancer cells (BCPAP cells) overexpressing the BRD9 gene, the results suggested that SCH772984 reverses the high expression of MAPK/ERK pathway-associated protein in BCPAP cells (over-expression BRD9 cells). In conclusion, this study demonstrated that BRD9 was highly expressed in serum and malignant tumor tissues of thyroid cancer patients and further promoted the development of the malignant phenotype of thyroid cancer by activating the MAPK/ERK signaling pathway.