RNA-binding protein NOVA1 promotes acute T-lymphocyte leukemia progression by stabilizing USP44 mRNA

Biochem Cell Biol. 2023 Oct 10. doi: 10.1139/bcb-2023-0092. Online ahead of print.ABSTRACTAcute T-lymphocyte leukemia (T-ALL) is a malignant tumor disease. RNA-binding protein Neotumor ventral antigen-1 (NOVA1) is highly expressed in bone marrow mononuclear cells of T-ALL patients, while its role in T-ALL progression remains unknown. Here, the gain- and loss-of-function studies for NOVA1 were performed using lentivirus-mediated NOVA1 overexpression/knockdown in Jurkat and CCRF-CEM cells. NOVA1 overexpression promoted cell proliferation and cell cycle progression. NOVA1 knockdown increased the apoptosis rate of T-ALL cells. Ubiquitin-specific protease 44 (USP44), a nuclear protein with deubiquitinase catalytic activity, has been reported to function as an oncogene in human T-cell leukemia. Expression of USP44 was positively regulated by NOVA1, and RNA Immunoprecipitation assay verified the binding of NOVA1 to the mRNA of USP44. USP44 knockdown partially abolished NOVA1-induced cell proliferation and inhibition of apoptosis. The in vivo xenograft experiment was performed by injection of T-ALL tumor cells into the tail vein of NOD/SCID mice. We found that cells with NOVA1 knockdown had lower tumorigenicity. NOVA1 knockdown alleviated pathological changes in lung and spleen tissues, and increased the overall survival period and the weight of T-ALL mice. Thus, NOVA1 acts as an accelerator in T-ALL, and its function is achieved by binding to and stabilizing USP44 mRNA.PMID:37816258...
Source: Biochemistry and Cell Biology - Category: Biochemistry Authors: Source Type: research