Zhang Wenjie, Long Jinlan, Tang Peixia, Chen Kaili, Guo Guangyao, Yu Zezhong, Lin Jie, Liu Liping, Zhan Rong, Xu Zhenshu
Fujian Provincial Key Laboratory on Hematology, Fujian Institute of Hematology, Fujian Medical University Union Hospital, 29 Xinquan Rd, Fuzhou, 350001, China.
Biomark Res. 2023 Jun 6;11(1):58. doi: 10.1186/s40364-023-00506-4.
Chronic lymphocytic leukemia (CLL) is one of the most frequent occurring types of leukemia. It typically occurs in elderly patients and has a highly variable clinical course. At present, the molecular mechanism driving the pathogenesis and progression of CLL is not fully understood. The protein Synaptotagmin 7 (SYT7) encoded by the SYT7 gene has been found to be closely related to the development of various solid tumors, but its role in CLL is unclear. In this study, we investigated the function and molecular mechanism of SYT7 in CLL.
The expression level of SYT7 in CLL was determined by immunohistochemical staining and qPCR. The role of SYT7 in promoting CLL development was verified by in vivo and in vitro experiments. The molecular mechanism of SYT7 in CLL was elucidated by methods such as GeneChip analysis and Co-immunoprecipitation assay.
Malignant behaviors such as proliferation, migration, and anti-apoptosis of CLL cells were significantly inhibited after SYT7 gene knockdown. In contrast, SYT7 overexpression promoted CLL development in vitro. Consistently, the knockdown of SYT7 also inhibited xenograft tumor growth of CLL cells. Mechanistically, SYT7 promoted CLL development by inhibiting SYVN1-mediated KNTC1 ubiquitination. The KNTC1 knockdown also attenuated the effects of SYT7 overexpression on development of CLL.
SYT7 regulates the progression of CLL through SYVN1-mediated KNTC1 ubiquitination, which has potential value for molecular targeted therapy of CLL.
慢性淋巴细胞白血病（CLL）是最常见的白血病类型之一。它通常发生于老年患者，临床病程高度可变。目前，驱动CLL发病机制和进展的分子机制尚未完全明确。由SYT7基因编码的蛋白质突触结合蛋白7（SYT7）已被发现与多种实体瘤的发生密切相关，但其在CLL中的作用尚不清楚。在本研究中，我们探究了SYT7在CLL中的功能及分子机制。
通过免疫组织化学染色和qPCR检测CLL中SYT7的表达水平。通过体内和体外实验验证SYT7在促进CLL发展中的作用。通过基因芯片分析和免疫共沉淀分析等方法阐明SYT7在CLL中的分子机制。
SYT7基因敲低后，CLL细胞的增殖、迁移和抗凋亡等恶性行为受到显著抑制。相反，SYT7过表达在体外促进了CLL的发展。同样，SYT7的敲低也抑制了CLL细胞的异种移植肿瘤生长。机制上，SYT7通过抑制SYVN1介导的KNTC1泛素化促进CLL的发展。KNTC1的敲低也减弱了SYT7过表达对CLL发展的影响。
SYT7通过SYVN1介导的KNTC1泛素化调节CLL的进展，这对CLL的分子靶向治疗具有潜在价值。
