DExD/H-box家族蛋白在肿瘤中的研究进展

人类DExD/H-box家族蛋白是一种重要的RNA解旋酶,在RNA的加工过程中发挥重要的作用,其生物学特点与功能有待深入研究.随着对RNA在生命进程中作用的研究,发现DExD/H-box家族蛋白作为一种重要的RNA解旋酶几乎涉及RNA生命进程(包括pre-mRNA剪接、核糖体生物合成、基因转录等)中的所有环节.近年来该家族在恶性肿瘤中的作用备受关注,研究发现其在肿瘤的发生发展中起重要作用.本文将对该家族蛋白在恶性肿瘤中的研究进展进行概述.     

P53翻译后修饰研究进展

肿瘤抑制基因p53在肿瘤发生中发挥着重要作用。P53蛋白的翻译后修饰及其与多种细胞蛋白间相互作用使P53蛋白呈现功能多样性。P53的翻译后修饰不是单个位点的修饰而是包括磷酸化、乙酰化、泛素化及SUMO化作用的多位点修饰。翻译后修饰对P53功能至关重要,更可能与某些肿瘤的发生密切相关。发生在蛋白质水平上的P53的功能性灭活是没有发生p53基因突变肿瘤发生的重要机制之一。     

MicroRNA-155 在免疫调控中的作用

<正>microRNAs(miRNAs)是一种具有高度保守序列的非编码微小RNA分子,能在转录后通过与靶基因的特异性相互作用来降解mRNA或者抑制靶基因的翻译,也可以在特定条件下上调靶基因的翻译和转录水平、microRNA-155与micRNA家族中的一员,介导多种生理病理过程,在炎症反应、免疫反应、肿瘤的发生和发展中发挥重要作用。现就miRNA-155的主要特点及其功能的研究进展予以综述。     

环状RNA ciRS-7的功能及调控机制研究进展

ciRS-7是一种特殊的环状RNA分子,在哺乳动物和人类的细胞中大量存在,在基因的转录与翻译中起到重要作用进而参与调控多种生命活动。ciRS-7是近年来RNA领域最新的研究热点。ciRS-7通过调控多条信号通路在细胞中发挥特定作用,将细胞外的分子信号经细胞膜传入细胞内发挥效应。ciRS-7富含MicroRNA(miRN...     

CD226分子在NK细胞杀伤肿瘤中的作用及其分子机制

在肿瘤免疫中,自然杀伤细胞(NK)和细胞毒性T细胞(CTL)均发挥十分重要的作用,而NK细胞的功能受到表面活化性和抑制性受体的调控.CD226,又名DNAX辅助分子( DNAM-1),是一种表达于NK细胞、CTL细胞和血小板等多种细胞表面的活化性受体,在NK细胞的活化和杀伤功能调控中发挥重要作用.近年研究发现,CD226不仅直接参与调控NK细胞的活化和杀伤功能,在控制肿瘤转移以及调控树突状细胞(DC)功能中也发挥重要作用.本文综述了CD226分子在NK细胞杀伤肿瘤细胞中的作用及其分子机制.     

CircRNA锌指RNA结合蛋白在恶性肿瘤中作用研究进展

环状RNA是一类具有特殊共价闭合环状结构的RNA分子,环状RNA锌指核糖核酸结合蛋白(circRNA-ZFR)在诸多恶性肿瘤中呈异常表达,并且其表达水平与肿瘤临床分期、癌细胞转移及患者预后密切相关;circRNA-ZFR可通过内源竞争性吸附miRNA、调节细胞周期、激活多种信号通路等机制参与调控肿瘤的发生发展。深入研究circRNA-ZFR在恶性肿瘤中的表达及作用机制有助于相关肿瘤的早期诊断、靶向治疗和患者预后评估。     

肿瘤靶向性RGD-IFN-α2a融合蛋白在原核细胞中的表达与纯化

RGD肽是一类含有精氨酸-甘氨酸-天冬氨酸(Arg-Gly-Asp)的短肽,作为整合素和其配体相互作用的识别位点,能与肿瘤细胞或肿瘤组织新生血管特异性高表达的某些整合素如αV β3结合,从而将治疗效应分子靶向性地导入肿瘤部位,有效减少肿瘤治疗中对正常组织细胞的损害,提高药物本身疗效[1].干扰素(interferon,IFN)是一类重要的细胞因子,具有抗病毒、抑制某些细胞生长、免疫调节、抑制和杀伤肿瘤细胞等多种作用,在临床上已被广泛用于恶性肿瘤与病毒疾病的治疗[2-3].增强型绿色     

德国科学家开发出分析蛋白质-RNA互作网络的新型工具

<正>据TRendel J 2018年12月6日(Cell,2018. DOI:10.1016/j.cell.2018.11.004)报道,德国癌症研究中心等机构的科学家们通过研究首次开发出了一种新方法,能帮助分析细胞中完整的RNA蛋白网络的组成情况。所有RNA分子在完成重要任务时都需要蛋白质作为结合伴侣,RNA分子在细胞中能发挥重要的作用,比如信使RNA分子(m RNA)能够帮助将储存在DNA中的遗传信息翻译成为蛋白质。然而,其他很多RNA分子的功能或许并不是翻译蛋白质,实际上,人类细胞中仅有5%RNA才是m RNA。     

长链非编码RNA LOXL1-AS1在人类恶性肿瘤中的作用及其分子调控机制

长链非编码RNA(lncRNA)广泛参与生物体的各种生理与病理过程。lncRNA作为肿瘤致癌因子或抑癌因子参与恶性肿瘤的多种生物过程，与恶性肿瘤的发生、发展密切相关。赖氨酰氧化酶样蛋白1-反义RNA1(LOXL1-AS1)是近年来发现的一种lncRNA,其在多种恶性肿瘤中表达上调，并与肿瘤大小、TNM分期、淋巴结转移、患者预后等病理特征相关。LOXL1-AS1通过与多种微小RNA竞争性结合，调节下游靶基因的表达及调控相关信号通路发挥促癌作用。该文通过总结LOXL1-AS1参与多种人类恶性肿瘤的生物学过程，不同的分子调控机制影响肿瘤细胞增殖、转移、侵袭和凋亡等恶性生物学行为，探讨潜在的临床意义和应用前景，以期为恶性肿瘤的临床诊断、治疗和筛选预后标志物提供理论基础和参考依据。     

长链非编码RNA低表达或表达缺失与恶性肿瘤发生的研究进展

长链非编码RNA(lncRNA)是指长度超过200个核苷酸的非编码RNA,其通过与DNA、RNA和蛋白质等分子相互作用,从表观遗传学、转录水平以及转录后水平等3个层面发挥重要调控作用.近年研究表明,lncRNAs在许多肿瘤的发生、发展过程中发挥着促癌或抑癌作用,部分lncRNAs因其特殊的生物学特性有希望成为新型肿瘤标记物和肿瘤治疗的新靶点.本文总结了近年来在肿瘤中低表达或呈表达缺失的lncRNAs,探讨其与肿瘤发生的相关机制,评价其在肿瘤诊断和治疗方面的临床应用前景.     

Inflammation-Related Carcinogenesis: Current Findings in Epidemiological Trends, Causes and Mechanisms

Inflammation is a definite cancer-causing factor as revealed by cumulative basic, clinical and epidemiological studies. It is mostly induced by infectious agents. For instance, infection with papillomaviruses associates with anogenital cancers, especially cervical cancers; Helicobacter pylori infection of the stomach tends to increase the risk of stomach cancer; chronic hepatitis B & C viruses and fluke infections of the liver increase liver cancers; autoimmune diseases, e.g., inflammatory bowel diseases, associate with development of colorectal cancer, and aerial irritants (foreign bodies) such as asbestos or fine particulate matter (PM_2.5) in outdoor air increase malignant pleural mesotheliomas or lung cancers. These are typical examples of inflammation-related carcinogenesis. It is apparent that the pathogens to induce inflammatory reactions in specific organs are not related to each other. However, the underlying pathogenesis in common is to induce and/or sustain inflammation. In this article, I would like to review the up-to-date findings of epidemiological trends, causes and mechanisms of inflammation-related carcinogenesis.     

Potential of interferon-alpha in solid tumours: part 2

The second part of this review examines the use of recombinant interferon-alpha (rIFNalpha) in the following solid tumours: superficial bladder cancer, Kaposi's sarcoma, head and neck cancer, gastrointestinal cancers, lung cancer, mesothelioma and ovarian, breast and cervical malignancies. In superficial bladder cancer, intravesical rIFNalpha has a promising role as second-line therapy in patients resistant or intolerant to intravesical bacille Calmette-Guérin (BCG). In HIV-associated Kaposi's sarcoma, rIFNalpha is active as monotherapy and in combination with antiretroviral agents, especially in patients with CD4 counts >200/mm(3), no prior opportunistic infections and nonvisceral disease. rIFNalpha has shown encouraging results when used in combination with retinoids in the chemoprevention of head and neck squamous cell cancers. It is effective in the chemoprevention of hepatocellular cancer in hepatitis C-seropositive patients. In neuroendocrine tumours, including carcinoid tumour, low-dosage (相似文献   

Crucial Roles of LncRNAs-Mediated Autophagy in Breast Cancer

Breast cancer remains a worldwide public health issue. LncRNA and autophagy respectively or simultaneously, get involved in cellular and molecular processes of many different cancers, including genesis, metastasis, and deterioration of breast cancer and other malignant tumors. In this review, relevant studies have been summarized, and we have found that lncRNA-mediated autophagy in luminal A breast cancer, luminal B breast cancer, HER-2 positive breast cancer, and basal-like breast cancer may play an important role in mediating drug resistance sensitivity. LncRNAs target genes and affect different signaling pathways to a complex network, which attenuates the occurrence and development of primary breast cancer by coordinating autophagy. Abnormal expression of LncRNA may lead to dysregulation of autophagy, resulting in tumor genesis, expansion, and resistance to anti-tumor therapy. Targeting specific lncRNAs for autophagy regulation may conduct as a bio-marker for reliable diagnosis and prognosis treatment of breast cancer or provide a promising therapeutic strategy.     

Probable implication of mutations of the X open reading frame in the onset of fulminant hepatitis B

A pathogenic role of precore-defective mutation in the onset of fulminant hepatitis B has been suggested. However, precore-defective mutants do not always cause fulminant hepatitis B and are not always isolated from affected patients. These findings strongly suggest the presence of some additional important mutations outside the precore region in fulminant hepatitis. In the present investigation an attempt was made to sequence the X open reading frame of hepatitis B virus DNA isolated from seven patients with fulminant hepatitis B and five patients with acute hepatitis B. The latter were used as controls. Since the X open reading frame encodes the X protein and contains the core promoter/enhancer II complex, some critical mutations may enhance or disrupt the replication and expression of hepatitis B virus DNA leading to fulminant hepatitis. A C-to-T substitution was found at nucleotide (nt) 1655, an A-to-T substitution at nt 1764 and a G-to-A substitution at nt 1766 in 4, 5 and 5 patients, respectively, out of the seven with fulminant hepatitis. These substitutions were not recognized in the patients with acute hepatitis. These mutations might change the function of the X protein and core promoter/enhancer II complex. It is suggested, therefore, that these mutations, as well as the precore-defective mutation, may play an important role in the pathogenesis of fulminant hepatitis. © Wiley-Liss, Inc.     

Nucleic acid modulation of gene expression: approaches for nucleic acid therapeutics against cancer

Most cancers are characterized by abnormal gene expression, which is thought to contribute to the pathogenesis and maintenance of the malignant phenotype; abnormal proliferation, maturation, and apoptosis. Silencing such genes would appear to be a rational approach to the therapy of cancer, and some preliminary clinical studies support this concept. Of the strategies available, the anti-mRNA gene silencing approach has attracted much attention and is the focus of this review. This strategy includes three types of agents: (1) single-stranded antisense oligonucleotides; (2) catalytically active oligonucleotides, such as ribozymes, and DNAzymes that possess inherent RNA cleaving activity; and (3) small interfering RNA (siRNA) molecules that induce RNA interference (RNAi). Among these agents, antisense oligonucleotides, especially phosphorothioate (PS) oligonucleotides, have been the most frequently used in clinical trials. In this article, we provide an overview of anti-mRNA gene silencing agents and their development for use as cancer therapeutics.     

Synchronous primary breast cancer and hepatocellular carcinoma in a male patient: a case report

Male breast cancer is a rare malignant disease characterized by hormonal imbalance. Hepatocellular carcinoma (HCC) is the most common neoplasm of the liver, and is generally correlated with hepatitis B or C virus-related cirrhosis. While to our knowledge a case with these two malignant diseases in a same male patient in the concomitant period is an exceptional event, rarely reported in literature. In this report, we present a case in which a Chinese patient with hepatitis B developed a tumor mass that originated from segment V of the liver and presented with right breast nodules at the same time. Synchronous mastectomy and hepatectomy were performed, and standard endocrine therapy and chemotherapy as adjuvant treatment were therefore followed. The diverse histogenesis of the two kinds of cancers highlights the need for us to investigate any common physiopathogenetic elements.     

Association between viral infections and post-transplant malignancies in renal transplant recipients

Immunosuppressive treatment is associated with an increased incidence of different malignant diseases. The etiology of posttransplant malignancies is multifactorial and includes decreased immune response to different viral infections, inappropriate removal of damaged cells, and impaired ability to repair DNA. EBV, HHV-8, Merkel cell virus, hepatitis B virus, hepatitis C virus and BK virus are all considered to be involved in the etiology of post-transplant malignancies. CMV has been considered as a potential causative factor in the development of colon cancer. However, current knowledge is mainly based on case reports. Further studies are needed to establish the causative role of different viruses in the etiology and pathogenesis of different malignant diseases in renal transplant population.