Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 Wen Yuan Road, Nanjing 210023, China.
Biochemistry. 2024 Oct 15;63(20):2609-2620. doi: 10.1021/acs.biochem.4c00359. Epub 2024 Sep 25.
Synaptotagmin 7 (SYT7), a member of the synaptotagmin family, exhibits high expression in various tumors and is closely associated with patient prognosis. The tight regulation of SYT7 expression assumes paramount significance in the progression of tumorigenesis. In this study, we detected a high GC content in the first 1000 bp of the promoter region of SYT7, suggesting a potential role of the G-quadruplex in its transcriptional regulation. Circular dichroism spectroscopy results showed that -187 to -172 bp sequence can form a typical parallel G-quadruplex structure, and site mutation revealed the critical role of the ninth guanine in its formation. Then, treatment of two ligands of G-quadruplex (TMPyP4 and Pyridostatin) reduced both the expression of SYT7 and subsequent tumor proliferation, demonstrating the potential of the G-quadruplex as a targeted therapy for tumors. By shedding light on the pivotal role of the G-quadruplex in regulating SYT7 transcription, our study not only advances our comprehension of this intricate regulatory mechanism but also emphasizes the significance of SYT7 in tumor proliferation. These findings collectively contribute to a more comprehensive understanding of the interplay between G-quadruplex regulation and SYT7 function in tumor development.
突触结合蛋白 7（SYT7）是突触结合蛋白家族的成员，在各种肿瘤中表达水平较高，与患者预后密切相关。SYT7 表达的严格调控对肿瘤发生的进展至关重要。在本研究中，我们在 SYT7 启动子区域的前 1000bp 中检测到高 GC 含量，表明 G-四链体在其转录调控中可能发挥作用。圆二色光谱结果表明，-187 到-172bp 序列可以形成典型的平行 G-四链体结构，而位点突变揭示了第九个鸟嘌呤在其形成中的关键作用。然后，两种 G-四链体配体（TMPyP4 和 Pyridostatin）的处理降低了 SYT7 的表达及其后续的肿瘤增殖，表明 G-四链体作为肿瘤靶向治疗的潜力。通过阐明 G-四链体在调节 SYT7 转录中的关键作用，我们的研究不仅提高了我们对这一复杂调控机制的理解，还强调了 SYT7 在肿瘤增殖中的重要性。这些发现共同促进了对 G-四链体调节和 SYT7 功能在肿瘤发展中的相互作用的更全面理解。
