Level of Murine DDX3 RNA Helicase Determines Phenotype Changes of Hepatocytes In Vitro and In Vivo

Autor:	Olga V. Sergeeva, Timofei S. Zatsepin, Anna Kosyreva, Varvara Varlamova, Tatiana O. Abakumova, Evgeniya Shcherbinina, Tatiana Prikazchikova, Ilia Kurochkin, Renata Ialchina
Rok vydání:	2021
Předmět:	0301 basic medicine RNA helicase Cell Survival QH301-705.5 RNA therapy liver Article Catalysis DEAD-box RNA Helicases Inorganic Chemistry Transcriptome Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation In vivo Animals cancer Biology (General) Physical and Theoretical Chemistry QD1-999 Molecular Biology Spectroscopy Mice Inbred BALB C Gene knockdown Chemistry Organic Chemistry Wnt signaling pathway General Medicine Cell cycle RNA Helicase A In vitro Computer Science Applications Cell biology Gene Expression Regulation Neoplastic 030104 developmental biology 030220 oncology & carcinogenesis Hepatocytes Female transcriptome
Zdroj:	International Journal of Molecular Sciences Volume 22 Issue 13 International Journal of Molecular Sciences, Vol 22, Iss 6958, p 6958 (2021)
ISSN:	1422-0067
DOI:	10.3390/ijms22136958
Popis:	DDX3 RNA helicase is intensively studied as a therapeutic target due to participation in the replication of some viruses and involvement in cancer progression. Here we used transcriptome analysis to estimate the primary response of hepatocytes to different levels of RNAi-mediated knockdown of DDX3 RNA helicase both in vitro and in vivo. We found that a strong reduction of DDX3 protein (> 85%) led to similar changes in vitro and in vivo—deregulation of the cell cycle and Wnt and cadherin pathways. Also, we observed the appearance of dead hepatocytes in the healthy liver and a decrease of cell viability in vitro after prolonged treatment. However, more modest downregulation of the DDX3 protein (60–65%) showed discordant results in vitro and in vivo—similar changes in vitro as in the case of strong knockdown and a different phenotype in vivo. These results demonstrate that the level of DDX3 protein can dramatically influence the cell phenotype in vivo and the decrease of DDX3, for more than 85% leads to cell death in normal tissues, which should be taken into account during the drug development of DDX3 inhibitors.
Databáze:	OpenAIRE
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