Metformin promotes survivin degradation through AMPK/PKA/GSK-3β-axis in non–small cell lung cancer

Metformin, a first-line antidiabetic drug, has been reported with anticancer activities in many types of cancer. However, its molecular mechanisms remain largely unknown. As a member of inhibitor of apoptosis proteins, survivin plays an important role in the regulation of cell death. In the present study, we investigated the role of survivin in metformin-induced anticancer activity in non–small cell lung cancer in vitro. Metformin mainly induced apoptotic cell death in A549 and H460 cell lines. It remarkably suppressed the expression of survivin, decreased the stability of this protein, then promoted its proteasomal degradation. Moreover, metformin greatly suppressed protein kinase A (PKA) activity and induced its downstream glycogen synthase kinase 3β (GSK-3β) activation. PKA activators, both 8-Br-cAMP and forskolin, significantly increased the expression of survivin. Consistently both GSK-3β inhibitor LiCl and siRNA restored the expression of survivin in lung cancer cells. Furthermore, metformin induced adenosine 5′-monophosphate-activated protein kinase (AMPK) activation. Suppression of the activity of AMPK with Compound C reversed the degradation of survivin induced by metformin, and meanwhile, restored the activity of PKA and GSK-3β. These results suggest that metformin kills lung cancer cells through AMPK/PKA/GSK-3β-axis–mediated survivin degradation, providing novel insights into the anticancer effects of metformin.     

KDM5D inhibit epithelial-mesenchymal transition of gastric cancer through demethylation in the promoter of Cul4A in male

Gastric cancer is one of the top causes of cancer-related death around the world, and poor prognosis of gastric cancer is due to the lack of early detection and effective treatment especially in male. Here, we first revealed the role of histone lysine-specific demethylase 5D (KDM5D) in gastric cancer in male. KDM5D was associated with the metastasis of gastric cancer because of its critical role in the epithelial-mesenchymal transition of gastric cancer cells. Downregulation of KDM5D in gastric cancer cells significantly increase the number of migrated or invaded cells due to the increasing expressions of mesenchymal markers. Downregulation of KDM5D also promotes tumor formation of gastric cancer cell in vivo. For mechanism, downregulation of KDM5D could inhibit the demethylation in the promoter of CUL4A, which lead to the increasing expression of ZEB1 and decreasing expressions of p21 and p53. Collectively, KDM5D performed its role in metastasis of gastric cancer through demethylation in the promoter of CUL4A, and it suggested us a novel target in gastric cancer treatment in male.     

糖类应答元件结合蛋白——葡萄糖信号途径中的转录因子

糖类应答元件结合蛋白(ChREBP)是2001年发现的葡萄糖信号途径中的一个新的候选转录因子,在哺乳动物体内可结合到糖酵解和脂肪合成酶相关基因启动子区的糖类应答元件(ChRE)上,激活这些基因的转录,并与SREBP-1c协同作用,调节糖酵解和脂肪合成酶相关基因的表达。该文介绍ChREBP的基因结构、表达调控、活性调节、生物学功能及其作用机制等的最新研究进展。     

High cell density and high expression of recombinant human ApoA-IMilano in Escherichia coli by twice temperature-shifted induction

The effect of temperature on the formation of recombinant protein, apolipoprotein A-I_Milano was investigated in the present study. The temperature of the initial growth phase was set at 30°C, while temperature variation in induction phase was arranged in three modes. High cell-density culture of Escherichia coli and high expression of recombinant human by twice temperature-shifted induction were carried out. Experimental results showed that ApoA-I_Milano reached 4.8 g/L with the final cell density of OD₆₀₀, 150. It was found that twice temperature-shifted induction could successfully avoid the effect of acetic acid on cell density and the expression of the product. The present study provides a basic procedure for the production of recombinant ApoA-I_Milano.     

植物异源多倍体进化中基因表达的变化

多倍化是植物物种进化的主要动力, 异源多倍体植物在形成早期发生着快速的基因表达变化。本文概述了异源多倍体植物中基因表达变化的特点, 包括基因的沉默、激活和部分同源基因表达水平的变化, 探讨了基因表达变化的分子机制和生物学意义, 并对研究中的问题进行了分析和展望。     

RNF8/RNF168信号通路在DNA损伤修复中的作用

细胞内DNA会受部分外界因素(如紫外辐射,电离辐射和化学毒素)和内部因素(如复制错误)的影响而发生损伤,包括DNA双链断裂、DNA错配和DNA交链等。DNA损伤发生后,损伤部位会被一些蛋白识别,进而招募一系列蛋白至损伤部位,形成一个修复系统。DNA双链断裂是最严重的一种DNA损伤,错误修复往往导致疾病的发生。DNA双链断裂(double strand break, DSB)后,细胞启动RNF8/RNF168信号通路进行修复。RNF8和RNF168是这条通路的枢纽蛋白;53BP和BRCA1是关键的效应蛋白,决定着DSB修复的方式;组蛋白泛素化、磷酸化和甲基化等翻译后修饰是这条通路顺利进行的基本条件;染色质重塑、泛素化酶/去泛素化酶平衡和蛋白稳定性是这条通路的主要调节方式。本综述对RNF8/RNF168信号通路进行了梳理总结,希望其能对相关研究者起到参考作用。     

基于16S基因序列海南产白唇竹叶青蛇的分类地位

为研究海南产白唇竹叶青蛇分类地位,捕捉来自海南岛各地的12个白唇竹叶青蛇样本,并从GenBank下载65个竹叶青蛇的样本序列,以瘤鼻蝮蛇为外群,建立16S系统发育树。系统发育树显示,竹叶青蛇分为多个属的观点具有很大的合理性,白唇竹叶青蛇隶属于帝汶(岛屿)竹叶青蛇属。进一步验证了经典形态学和生物地理学的观点,海南岛产白唇竹叶青与其它地方产白唇竹叶青蛇不存在生殖隔离。     

中国生物多样性在线数据处理平台的构建

高质量的生物多样性数据能够为生物多样性的研究与保护提供数据支撑。目前研究人员开发了大量的生物多样性数据处理软件或工具, 包括工作流系统、R语言包、Python语言包和Excel工具等, 但是使用这些软件或工具需要用户安装相应的软件客户端, 并掌握一定的编程语言、软件开发和复杂的Excel公式等知识和技能。为降低用户的学习成本和使用门槛, 本文采用了Browser/Server模式设计技术、Web技术、可视化技术、响应式开发技术、网络爬虫技术、数据处理技术和Solr智能检索技术等, 针对不同维度的生物多样性数据设计和开发了相应的数据处理模块, 构建了中国生物多样性在线数据处理平台(http://dp.iflora.cn/)。该平台能够有效地帮助科研人员对物种名称、地理位置、时间日期和经纬度等数据进行处理, 并提供数据格式转换、数据质量评测和资源统计分析等辅助功能, 帮助科研人员实现零代码和低门槛地处理生物多样性数据, 提供便捷、高效和简单的数据清洗、校正、转换和整合等数据处理渠道, 为生物多样性研究和保护提供信息化技术支持与服务。