DHX33 mediates p53 to regulate mevalonate pathway gene transcription in human cancers

• Published in: Biochimica et biophysica acta. General subjects Vol. 1868; no. 3; p. 130547
• Main Authors: Nie, Guangli, Chen, Shiyun, Song, Qingzhi, Zou, Dongxu, Li, Maggie, Tang, Xiyu, Deng, Yuanlian, Huang, Bizhou, Yang, Mengxia, Lv, Guoqing, Zhang, Yandong
• Format: Journal Article
• Language: English
• Published: Netherlands 01.03.2024
• Subjects: Animals; Carcinogenesis; DEAD-box RNA Helicases - genetics; Humans; Lung - metabolism; Mevalonic Acid; Mice; Transcription, Genetic; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; DHX33; RAS; Mevalonate pathway; RNA helicase; p53
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2023.130547

Tumor suppressor p53 is frequently null or mutated in human cancers. Here in this study, DHX33 protein was found to be induced in p53 null cells in vitro, and in p53 mutant lung tumorigenesis in vivo. Cholesterol metabolism through mevalonate pathway is pivotal for cell proliferation and is frequently altered in human cancers. Mice carrying mutant p53 and Kras alleles showed upregulation of mevalonate pathway gene expression. However upon DHX33 loss, their upregulation was significantly debilitated. Additionally, in many human cancer cells, DHX33 knockdown caused inhibition of mavelonate pathway gene transcription. We propose DHX33 locates downstream of mutant p53 and Ras to regulate mevalonate pathway gene transcription and thereby supports cancer development in vivo.