miR-20b-5p在肿瘤及其他疾病中的生物学功能

miRNAs是一类非编码的小RNA分子,在多种疾病的发病和治疗中发挥重要作用,可调控细胞增殖、细胞周期、凋亡和迁移等过程中关键基因的表达。miR-20b-5p属于miR-17家族,在多种肿瘤中和非肿瘤性疾病中存在异常表达。在肿瘤中,miR-20b-5p扮演着癌基因或抑癌基因的角色,可通过调控相应靶分子的表达影响肿瘤细胞的增殖、凋亡、侵袭与迁移等生物学行为,进而促进或抑制肿瘤的发生发展。该文对miR-20b-5p在肿瘤和非肿瘤性疾病中的生物学功能和机制进行简要综述。相信随着对miR-20b-5p的功能和机制的深入阐明,miR-20b-5p有望作为多种疾病的诊治靶点。     

程序性细胞死亡分子5(PDCD5)研究进展

程序性细胞死亡分子5(programmed cell death 5,PDCD5)在人体各种组织中广泛存在,可以通过多种凋亡通路促进细胞凋亡,其在大部分肿瘤中低表达,对肿瘤化疗具有增敏效应.近年发现,除了在细胞凋亡过程中发挥作用外,PDCD5在多种疾病的病理进程中发挥重要作用,如:肿瘤、自身免疫性疾病、炎症性疾病、脑缺...     

组蛋白甲基转移酶SMYD家族与肿瘤

组蛋白甲基化修饰是肿瘤表观遗传学修饰异常的研究热点。这种修饰涉及肿瘤细胞的生物学行为,并参与肿瘤发生、发展和病理转归。含有SET结构域和MYND结构域蛋白的SMYD家族,是一组重要的赖氨酸甲基转移酶,主要通过组蛋白或非组蛋白甲基化修饰,调控其下游靶基因和肿瘤关键信号通路,参与肿瘤发生和发展的整个过程。SMYD家族影响肿瘤细胞的增殖、分化、凋亡、血管形成、侵袭和转移以及化疗敏感性等生物学特性。SMYD家族成员作为肿瘤新型分子诊断标志物和治疗靶点,有着巨大的临床应用价值和意义。本文综述了SMYD家族在肿瘤中的转录调控机制、生物学功能、临床研究意义及其作为分子靶点的抗肿瘤新药研究。     

鞘氨醇激酶-磷酸鞘氨醇轴在血管生成相关性疾病中的作用

血管生成是指在原有血管的基础上形成新血管的过程。病理性血管生成是癌症、心血管类疾病和视网膜病变等一系列疾病的标志。1-磷酸鞘氨醇(sphingosine-1-phosphate,S1P)是一种信号脂质,由鞘氨醇激酶（sphingosine kinases,SPHK）合成,通过5种G蛋白偶联受体(sphingosine-1-phosphate receptors,S1PR1-5)发挥其不同的生物学和病理生理作用,并通过激活受体启动各种信号级联反应,影响细胞命运、血管张力、内皮功能和完整性以及淋巴细胞的运输等。其产生和信号的失衡与内皮功能障碍和异常血管生成等病理过程密切相关。越来越多的证据表明, SPHK-S1P轴在血管生成中发挥重要作用,尤其在癌症的发生发展与肿瘤微环境、动脉粥样硬化、心肌梗死等心血管类疾病,以及糖尿病和视网膜病变中具有重要意义。研究其相关作用与功能,可为治疗血管生成相关疾病提供新见解和药物治疗靶点。本文就SPHK-S1P轴通过SPHK以及S1PR1-5影响内皮细胞和平滑肌增殖、内皮细胞迁移以及由内皮细胞、周细胞和平滑肌细胞等形成管腔的分子机制进行阐述,同时进一步阐述SPHK-S1P轴如何通过鞘氨醇激酶以及S1PR1-5影响肿瘤、心血管类疾病、糖尿病以及视网膜病变中血管生成,旨在通过理解SPHK-S1P轴在血管生成中的分子机制为相关疾病提供新的治疗思路。     

Wnt5a及其信号通路与血管新生的研究进展

Wnt5a是Wnt蛋白家族中的成员之一,在细胞成熟、胚胎发育等过程中发挥着重要作用。研究表明Wnt5a的表达调控及其信号通路与血管新生密切相关,并且在血管新生性相关疾病中发挥了重要作用。本文从Wnt5a与其相关信号转导通路对血管新生的影响以及分子机制等方面进行阐述和展望,旨在为以Wnt5a为靶点进行血管新生性疾病的防治提供理论依据。     

非肌肉肌球蛋白ⅡA的相互作用蛋白研究进展

非肌肉肌球蛋白ⅡA(NMⅡA)是肌球蛋白超家族的成员之一,其生物学功能已引起国内外学者的广泛重视。研究发现,NMⅡA可作为分子马达为细胞内分子运动提供动力;还可通过与其他蛋白质发生相互作用而参与细胞黏附与迁移、细胞吞噬、胞质分裂等多种生理病理活动。本文综述了与NMⅡA存在相互作用的蛋白质及其产生的生物学效应,以期为全面了解NMⅡA的生理病理功能,深入探讨肿瘤等重大疾病的发病机制及新药研发提供一定线索和依据。     

间充质干细胞在恶性肿瘤生物学中作用的研究进展

过去近半个世纪的研究表明,间充质干细胞(MSCs)作为肿瘤微环境中细胞成份的重要成员之一,它在肿瘤细胞生长增殖、凋亡调控、侵袭性生长和转移、血管新生、能量代谢以及治疗抗性等诸多恶性生物学特性中均发挥重要的生物学作用,其相关的分子机制也逐步被揭示;相应地,基于这些发现的基因工程修饰和物理(化学)预处理的MSCs在特定肿瘤综合治疗中临床应用研究也取得了令人振奋的结果。本文就目前MSCs在恶性肿瘤发生发展中所起的生物学作用及其分子机制研究的相关进展作一综述,并就未来MSCs相关的新研究方向及其肿瘤综合治疗中可能的临床应用作一简单的展望。     

肿瘤坏死因子α诱导蛋白8的生物学效应及其临床价值北大核心CSCD

肿瘤坏死因子α诱导蛋白8(tumor necrosis factor alpha induced protein-8,TNFAIP8)作为TNFAIP8家族的成员之一,被认为是一种具有抗凋亡和促肿瘤效应的蛋白分子,在细胞的存活和死亡中发挥重要作用。本文重点介绍TNFAIP8的发现过程、结构功能、生物学效应及其临床意义,并对其可能的作用机制进行概述。     

成纤维细胞生长因子5的研究进展

成纤维细胞生长因子5 (fibroblast growth factor 5,FGF5)是成纤维细胞生长因子家族(FGFs)的成员之一,在哺乳动物毛囊、神经系统、睾丸等多个部位及胚胎发育过程中均有表达。研究发现,FGF5具有广泛的生物学活性,如作为毛发生长重要的调节因子其编码基因突变将导致毛发异常生长,作为丝裂原在干细胞增殖、血管生成和肢体肌发育等方面发挥重要作用,以及在高血压、肿瘤等方面具有重要的生物学功能。目前,FGF5在多种疾病中的功能和作用机制尚需进一步深入研究,但其在毛发生长、干细胞增殖及在心血管疾病等方面的生物学作用具有重大的意义和临床应用价值。总结了近些年FGF5的研究进展,系统阐述了FGF5在毛发生长、干细胞增殖分化、心血管疾病及癌症等方面的相关作用机制,为进一步深入研究FGF5在疾病治疗中的作用和开发利用提供参考。     

Caveolin家族分子研究进展

Caveolae是近年新认识的一种膜特异性微区结构,caveolin分子是形成caveolae所必需的重要结构蛋白。近几年人们对caveolin分子结构和功能的认识获得较大进展,特别是其参与跨膜信号转导和调节、细胞胆固醇转运以及与肿瘤发生相关等方面尤其引起人们重视。本文对caveolin分子家族成员的基因定位、分子特性、生物学功能以及该分子与疾病的关联进行了综述。     

miR-192/215-5p act as tumor suppressors and link Crohn's disease and colorectal cancer by targeting common metabolic pathways: An integrated informatics analysis and experimental study

MicroRNAs have emerged as key regulators involved in a variety of biological processes. Previous studies have demonstrated that miR-192/215 participated in progression of Crohn's disease and colorectal cancer. However, their concrete relationships and regulation networks in diseases remain unclear. Here, we used bioinformatics methods to expound miR-192/215-5p macrocontrol regulatory networks shared by two diseases. For data mining and figure generation, several miRNA prediction tools, Human miRNA tissue atlas, FunRich, miRcancer, MalaCards, STRING, GEPIA, cBioPortal, GEO databases, Pathvisio, Graphpad Prism 6 software, etc . are extensively applied. miR-192/215-5p were specially distributed in colon tissues and enriched biological pathways were closely associated with human cancers. Emerging role of miR-192/215-5p and their common pathways in Crohn's disease and colorectal cancer was also analyzed. Based on results derived from multiple approaches, we identified the biological functions of miR-192/215-5p as a tumor suppressor and link Crohn's disease and colorectal cancer by targeting triglyceride synthesis and extracellular matrix remodeling pathways.     

Molecular dissection of the membrane aggregation mechanisms induced by monomeric annexin A2

Annexins are a multigene family of proteins involved in aggregation and fusion processes of biological membranes. One of its best-known members is annexin A2 (or p36), capable of binding to acidic phospholipids in a calcium-dependent manner, as occurs with other members of the same family. In its heterotetrameric form, especially with protein S100A10 (p11), annexin A2 has been involved as a determinant factor in innumerable biological processes like tumor development or anticoagulation. However, the subcellular coexistence of different pools of the protein, in which the monomeric form of annexin A2 is growing in functional relevance, is to date poorly described. In this work we present an exhaustive structural and functional characterization of monomeric human annexin A2 by using different recombinant mutants. The important role of the amphipathic N-terminal α-helix in membrane binding and aggregation has been analyzed. We have also studied the potential implication of lateral “antiparallel” protein dimers in membrane aggregation. In contrast to what was previously suggested, formation of these dimers negatively regulate aggregation. We have also confirmed the essential role of three lysine residues located in the convex surface of the molecule in calcium-free and calcium-dependent membrane binding and aggregation. Finally, we propose models for annexin A2-mediated vesicle aggregation mechanisms.     

肿瘤细胞来源的外泌体与恶性肿瘤的进展及化疗

外泌体是细胞分泌的一种纳米级囊泡结构,在血液、唾液、尿液等多种体液中均有分布.作为一类重要的细胞间通信分子,外泌体含有多种具有生物活性的成分,可通过多种方式在人体中发挥调节作用.目前在多种类型的细胞中均发现外泌体的存在,而肿瘤细胞来源的外泌体由于其本身的特性和功能特点,可通过微环境介导肿瘤细胞的增生、血管形成和免疫耐受,并可通过介导上皮-间质转化（epithelial-mesenchymal transition, EMT）
和胞内药物排斥反应等增加肿瘤细胞的化疗抵抗能力.同时,因其含有肿瘤细胞所分泌的特异性成分,因而可通过对外泌体中相关分子改变的检测,对疾病进行诊断和监测,并可为临床个体化用药提供新思路.     

SIRT3与细胞代谢及心血管疾病的相关性

蛋白去乙酰化酶在细胞生理过程中发挥着极为重要的作用。人蛋白去乙酰化酶包括HDACⅠ、HDACⅡ、HDACⅢ和HDACⅣ4个家族。其中第Ⅲ类即Sir2(Silent information regulator 2)家族包括7个成员——SIRT1~ SIRT7,每个成员都具有不同的细胞定位,并且发挥不同的生物学功能。作为主要定位于线粒体的组蛋白去乙酰化酶,SIRT3不仅调节细胞的能量代谢,并在细胞凋亡、肿瘤生长和一些疾病中发挥作用。文章综述了SIRT3在细胞代谢中的生物学功能以及其在心血管疾病中的研究进展。     

泌乳素及其受体的研究进展

泌乳素(PRL)又名催乳素,是由腺垂体及一些垂体外器官如乳腺、胸腺、脾脏等合成的一种多肽类激素,以内分泌、自分泌、旁分泌的形式发挥作用,其广泛参与机体生长发育、物质代谢、性腺功能调节、应激反应、免疫调节等。泌乳素通过与其受体(PRL receptor,PRLR)在靶细胞的细胞膜表面结合,激活下游的信号转导通路,发挥其生物学作用。由于泌乳素在人体内复杂的生物学效应,泌乳素及其受体又与乳腺癌、泌乳素瘤等多种疾病的发生发展及其预后密切相关。本文就泌乳素发挥效应时对其受体的激活、受体激活后的信号转导机制以及泌乳素同相关疾病的联系进行了综述,相信泌乳素及其受体的研究将为这些疾病的治疗提供重要的方向。     

The annexinopathies: a new category of diseases

The annexins are a family of highly homologous phospholipid binding proteins, which share a four-domain structure, with one member of the family - annexin VI - having a duplication consisting of eight domains. Thus far, ten annexins have been described in mammals. Although the biological functions of the annexins have not been definitively established, two human diseases involving annexin abnormalities ('annexinopathies') have been identified as of the time of writing. Overexpression of annexin II occurs in the leukocytes of a subset of patients having a hemorrhagic form of acute promyelocytic leukemia. Underexpression of annexin V occurs on placental trophoblasts in the antiphospholipid syndrome and in preeclampsia. Also, an animal model has been described in which annexin VII is underexpressed and is associated with disease, but the relevance of this animal model to human disease is not yet understood. Future research is likely to elucidate additional 'annexinopathies'.     

Differential expression of annexins I and II in normal and malignant human mammary epithelial cells

Abstract. Collagen-binding proteins ( CBPs ) of rat mammary tumors are identical to Ca²⁺-binding annexins [49]. We have now isolated a protein of 38 kDa from the human mammary tumor cell line ALAB by collagen type I affinity chromatography as well as by extraction of calcium-binding proteins. The 38-kDa band of both preparations was identified as annexin II (calpactin I) by its reaction with an annexin II-specific monoclonal antibody in Western blot analysis. Annexin I (lipocortin I) was not detectable in these cells. Two other human cell lines, the SV40-transformed cell line SV3 and cell line HBL-100, both established from normal mammary glands, were also positive for annexin II and negative for annexin I.
In vivo expression of annexins was investigated by immunohistological staining of normal and malignant human mammary tissue. The annexin II-specific mAb reacted with normal and tumor parenchyme whereas the annexin I-specific mAb reacted with acini and ductal myoepithelium of the normal mammary gland but showed no reaction with tumor tissue. Immunolocalization studies also showed annexin II expression in both normal and tumor stroma while only tumor stromal cells were found to be reactive with the antibody against annexin I. The differential expression of annexins in normal and malignant human mammary tissue suggests special functions of these proteins in the mammary gland.     

Role of haem oxygenase-1 in microbial host defence

Haem oxygenase (HO)-1 is a cytoprotective enzyme that plays a critical role in defending the body against oxidant-induced injury during inflammatory processes. HO catalydes the degradation of haem to carbon monoxide (CO), biliverdin and ferrous iron. Biliverdin is converted to bilirubin, a potent endogenous antioxidant. CO has a number of biological functions, including anti-inflammatory properties. In various models of disease, HO-1 is known to play a critical role by ameliorating the pathological consequences of injury. In many of these models, the beneficial effects of HO-1 and its products of haem catabolism are by suppressing an inflammatory response. However, when investigating diseases due to microbial infections, inhibition of the inflammatory response could disrupt the ability of the immune system to eradicate an invading pathogen. Thus, questions remain regarding the role of HO-1 in microbial host defence. This microreview will address our present understanding of HO-1 and its functional significance in a variety of microbial infections.     

FGF/FGFR signaling: From lung development to respiratory diseases

The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling system regulates a variety of biological processes, including embryogenesis, angiogenesis, wound repair, tissue homeostasis, and cancer. It exerts these regulatory functions by controlling proliferation, differentiation, migration, survival, and metabolism of target cells. The morphological structure of the lung is a complex tree-like network for effective oxygen exchange, and the airway terminates in the middle and distal ends of many alveoli. FGF/FGFR signaling plays an important role in the pathophysiology of lung development and pathogenesis of various human respiratory diseases. Here, we mainly review recent advances in FGF/FGFR signaling during human lung development and respiratory diseases, including lung cancer, acute lung injury (ALI), pulmonary arterial hypertension (PAH), chronic obstructive pulmonary disease (COPD), asthma, and pulmonary fibrosis.     

MitProNet: A Knowledgebase and Analysis Platform of Proteome,Interactome and Diseases for Mammalian Mitochondria

Mitochondrion plays a central role in diverse biological processes in most eukaryotes, and its dysfunctions are critically involved in a large number of diseases and the aging process. A systematic identification of mitochondrial proteomes and characterization of functional linkages among mitochondrial proteins are fundamental in understanding the mechanisms underlying biological functions and human diseases associated with mitochondria. Here we present a database MitProNet which provides a comprehensive knowledgebase for mitochondrial proteome, interactome and human diseases. First an inventory of mammalian mitochondrial proteins was compiled by widely collecting proteomic datasets, and the proteins were classified by machine learning to achieve a high-confidence list of mitochondrial proteins. The current version of MitProNet covers 1124 high-confidence proteins, and the remainders were further classified as middle- or low-confidence. An organelle-specific network of functional linkages among mitochondrial proteins was then generated by integrating genomic features encoded by a wide range of datasets including genomic context, gene expression profiles, protein-protein interactions, functional similarity and metabolic pathways. The functional-linkage network should be a valuable resource for the study of biological functions of mitochondrial proteins and human mitochondrial diseases. Furthermore, we utilized the network to predict candidate genes for mitochondrial diseases using prioritization algorithms. All proteins, functional linkages and disease candidate genes in MitProNet were annotated according to the information collected from their original sources including GO, GEO, OMIM, KEGG, MIPS, HPRD and so on. MitProNet features a user-friendly graphic visualization interface to present functional analysis of linkage networks. As an up-to-date database and analysis platform, MitProNet should be particularly helpful in comprehensive studies of complicated biological mechanisms underlying mitochondrial functions and human mitochondrial diseases. MitProNet is freely accessible at http://bio.scu.edu.cn:8085/MitProNet.