Acute 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 the role of NOVA1 in T-ALL progression remains unknown. The gain- and loss-of-function studies for NOVA1 were performed 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 play an oncogene role in human T-cell leukemia. USP44 expression was positively associated with 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. The knockdown of NOVA1 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 might be achieved by binding to and stabilizing USP44 mRNA.

中文翻译：

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RNA 结合蛋白 NOVA1 通过稳定 USP44 mRNA 促进急性 T 淋巴细胞白血病进展。

急性T淋巴细胞白血病（T-ALL）是一种恶性肿瘤疾病。RNA结合蛋白新肿瘤腹侧抗原1（NOVA1）在T-ALL患者的骨髓单个核细胞中高表达，但NOVA1在T-ALL进展中的作用仍不清楚。NOVA1 的功能获得和丧失研究是在 Jurkat 和 CCRF-CEM 细胞中进行的。NOVA1 过表达促进细胞增殖和细胞周期进展。NOVA1 敲除增加了 T-ALL 细胞的凋亡率。泛素特异性蛋白酶 44 (USP44) 是一种具有去泛素酶催化活性的核蛋白，据报道在人类 T 细胞白血病中发挥癌基因作用。USP44的表达与NOVA1呈正相关，RNA免疫沉淀实验验证了NOVA1与USP44 mRNA的结合。USP44 敲低部分消除了 NOVA1 诱导的细胞增殖和细胞凋亡抑制。通过将T-ALL肿瘤细胞注射到NOD/SCID小鼠的尾静脉中进行体内异种移植实验。NOVA1 的敲低具有较低的致瘤性。NOVA1敲低减轻了肺和脾组织的病理变化，并增加了T-ALL小鼠的总生存期和体重。因此，NOVA1 在 T-ALL 中充当促进剂的作用，其功能可能是通过结合并稳定 USP44 mRNA 来实现的。