Role of DHX33 in c-Myc-induced cancers

Carcinogenesis
Jijun FuYandong Zhang

Abstract

Oncogene c-Myc is frequently amplified and activated in human cancers. Deregulation of c-Myc protein has been shown to occur in 30% of all human cancers, especially in hematopoietic malignancies. As a transcription factor, c-Myc has been shown to regulate up to 15% of all human genome genes, controlling diverse cellular activities including cell cycle, ribosome biogenesis, protein synthesis, metabolism, apoptosis and angiogenesis. In this report, we provide evidence that the RNA helicase DHX33 is a critical downstream target of c-Myc. Myc binds to DHX33 upstream promoter region and stimulates its transcription. Elevated DHX33 protein is pivotal for c-Myc to drive tumor formation. Knockdown of DHX33 to basal levels in c-Myc overexpressing cells significantly reduced cell proliferation, cell migration and anchorage-independent cell growth in vitro and in vivo. Additionally, we found that DHX33 promotes MMP9, MMP14 and urokinase-type plasminogen activator (PLAU) transcription by directly binding to their promoters, thus promoting cancer cell migration. DHX33 protein was overexpressed in a certain subset of human non-Hodgkin's lymphoma tissues. Finally, knockdown of DHX33 significantly inhibits the development of Myc-induced acute ...Continue Reading

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Citations

Jun 12, 2019·Molecular and Cellular Biology·Jiuling WangYandong Zhang
Jul 4, 2020·Journal of Cellular Physiology·Cheng PengYandong Zhang
Aug 9, 2020·Cancer Science·Xingshun WangYandong Zhang
Jan 27, 2019·Journal of Cellular Physiology·Dan SuYandong Zhang
Apr 22, 2020·Molecular and Cellular Biology·Weimin FengYandong Zhang
Apr 4, 2021·International Journal of Molecular Sciences·Olga Sergeeva, Timofei Zatsepin
Jun 6, 2018·Biochemistry·Xingshun WangYandong Zhang

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