Transcription factor NFYA promotes G1/S cell cycle transition and cell proliferation by transactivating cyclin D1 and CDK4 in clear cell renal cell carcinoma

Yu Li; Xing Xiao; Hengxing Chen; Zhen Chen; Kaishun Hu; Dong Yin

Transcription factor NFYA promotes G1/S cell cycle transition and cell proliferation by transactivating cyclin D1 and CDK4 in clear cell renal cell carcinoma

Am J Cancer Res. 2020 Aug 1;10(8):2446-2463. eCollection 2020.

Authors

Yu Li¹, Xing Xiao², Hengxing Chen¹, Zhen Chen¹, Kaishun Hu¹, Dong Yin¹

Affiliations

¹ Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou 510120, Guangdong, China.
² Department of Dermatology, Shenzhen Children's Hospital Shenzhen 518000, Guangdong, China.

PMID: 32905496
PMCID: PMC7471361

Abstract

NFYA (nuclear transcription factor Y, subunit A) is a CCAAT-binding transcription factor. Accumulating evidence suggests that NFYA plays an important role in breast, ovarian, lung and gastric cancer. However, the role of NFYA in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, it was discovered that the expression of NFYA is elevated in tissues of ccRCC patient and high NFYA expression is linked to poor overall survival in ccRCC patient. Inhibition of G1/S cell cycle transition and decreased cell proliferation were observed upon NFYA knockdown in ccRCC cells. Moreover, further investigation revealed that NFYA binds directly to the promoter region of both CDK4 and cyclin D1 (CCND1) thus transactivating their expression, resulting in RB phosphorylation and the activation of subsequent E2F pathway activation. Taken together, these findings imply the oncogenic role of NFYA in ccRCC progression and its potential as a target for ccRCC therapy.

Keywords: CDK4; G1/S transition; NFYA; ccRCC; cyclin D1.