G-Quadruplex-Mediated Transcriptional Regulation of SYT7: Implications for Tumor Progression and Therapeutic Strategies

IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Ying Ma, Jiarong Guo, Xinyi Song, Haipeng Rao, Jinxin Zhang, Miao Miao, Feiyan Pan* and Zhigang Guo*, 
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Abstract

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.

Abstract Image

G-四叠体介导的 SYT7 转录调控:对肿瘤进展和治疗策略的影响
突触表位素7(SYT7)是突触表位素家族的成员之一,在多种肿瘤中表现出高表达,并与患者的预后密切相关。SYT7表达的严格调控在肿瘤发生过程中具有重要意义。在本研究中,我们检测到 SYT7 启动子区域前 1000 bp 的 GC 含量较高,这表明 G-四联体在其转录调控中可能发挥作用。圆二色性光谱分析结果表明,-187 至 -172 bp 序列可形成典型的平行 G-四联体结构,位点突变揭示了第九个鸟嘌呤在其形成过程中的关键作用。随后,G-四联体的两种配体(TMPyP4和Pyridostatin)的处理降低了SYT7的表达和随后的肿瘤增殖,证明了G-四联体作为肿瘤靶向治疗的潜力。我们的研究揭示了G-四联体在调控SYT7转录中的关键作用,不仅加深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作用。这些发现有助于我们更全面地了解肿瘤发生过程中 G-四叠体调控与 SYT7 功能之间的相互作用。
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来源期刊
Biochemistry Biochemistry
Biochemistry Biochemistry 生物-生化与分子生物学
CiteScore
5.50
自引率
3.40%
发文量
336
审稿时长
1-2 weeks
期刊介绍: Biochemistry provides an international forum for publishing exceptional, rigorous, high-impact research across all of biological chemistry. This broad scope includes studies on the chemical, physical, mechanistic, and/or structural basis of biological or cell function, and encompasses the fields of chemical biology, synthetic biology, disease biology, cell biology, nucleic acid biology, neuroscience, structural biology, and biophysics. In addition to traditional Research Articles, Biochemistry also publishes Communications, Viewpoints, and Perspectives, as well as From the Bench articles that report new methods of particular interest to the biological chemistry community.
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