College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, Korea.
Department of Otolaryngology-Head and Neck Surgery, Center for Thyroid Cancer, Research Institute and Hospital, National Cancer Center, Goyang 10408, Korea.
BMB Rep. 2023 Sep;56(9):508-513. doi: 10.5483/BMBRep.2023-0051.
The phytochemical quercetin has gained attention for its antiinflammatory and anti-tumorigenic properties in various types of cancer. Tumorigenesis involves the aberrant regulation of kinase/phosphatase, highlighting the importance of maintaining homeostasis. Dual Specificity Phosphatase (DUSP) plays a crucial role in controlling the phosphorylation of ERK. The current study aimed to clone the DUSP5 promoter, and investigate its transcriptional activity in the presence of quercetin. The results revealed that quercetin-induced DUSP5 expression is associated with the serum response factor (SRF) binding site located in the DUSP5 promoter. The deletion of this site abolished the luciferase activity induced by quercetin, indicating its vital role in quercetin-induced DUSP5 expression. SRF protein is a transcription factor that potentially contributes to quercetin-induced DUSP5 expression at the transcriptional level. Additionally, quercetin enhanced SRF binding activity without changing its expression. These findings provide evidence of how quercetin affects anti-cancer activity in colorectal tumorigenesis by inducing SRF transcription factor activity, thereby increasing DUSP5 expression at the transcriptional level. This study highlights the importance of investigating the molecular mechanisms underlying the anti-cancer properties of quercetin, and suggests its potential use in cancer therapy. [BMB Reports 2023; 56(9): 508-513].
植物化学物质槲皮素因其在各种癌症中的抗炎和抗肿瘤特性而受到关注。肿瘤发生涉及激酶/磷酸酶的异常调节，这凸显了维持体内平衡的重要性。双特异性磷酸酶（DUSP）在控制 ERK 的磷酸化中起着至关重要的作用。本研究旨在克隆 DUSP5 启动子，并研究其在槲皮素存在下的转录活性。结果表明，槲皮素诱导的 DUSP5 表达与位于 DUSP5 启动子中的血清反应因子（SRF）结合位点有关。该位点的缺失消除了槲皮素诱导的荧光素酶活性，表明其在槲皮素诱导的 DUSP5 表达中具有重要作用。SRF 蛋白是一种转录因子，可能在转录水平上有助于槲皮素诱导的 DUSP5 表达。此外，槲皮素增强了 SRF 结合活性，而不改变其表达。这些发现提供了证据，说明槲皮素如何通过诱导 SRF 转录因子活性来影响结直肠肿瘤发生中的抗癌活性，从而在转录水平上增加 DUSP5 的表达。本研究强调了研究槲皮素抗癌特性的分子机制的重要性，并表明其在癌症治疗中的潜在用途。[BMB 报告 2023；56(9):508-513]。
