长链非编码RNA在消化系统肿瘤中的研究进展

长链非编码RNA（lncRNA）是一系列广泛转录自人及其他哺乳动物基因组的长度超过200 nt的核苷酸片段,通常没有蛋白编码功能,一度被认为是基因组的转录“噪音”。近年来一些 lncRNA 被发现具有多种生物学功能,成为分子生物学领域研究的热点。已经在多种肿瘤中发现有lncRNA的异常表达,并且异常表达的 lncRNA 和肿瘤的复发、转移及预后有关。本文中将探讨近期发现的与消化系统肿瘤相关的lncRNA,部分着重于具有促癌作用的lncRNA,以期为消化系统肿瘤的诊断、预后及分子治疗提供线索。     

The emerging regulatory roles of long non-coding RNAs implicated in cancer metabolism

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人脂肪干细胞脂向分化中长非编码RNA的差异表达

背景：肥胖导致了包括高血压、冠心病、脂肪肝、高脂血症、2型糖尿病在内的诸多疾病,因此深入理解脂肪细胞分化机制对于肥胖的防治具有深远意义。目前对于脂向分化机制的研究多集中在微小RNA上,对于长非编码RNA在脂向分化过程中的作用尚且知之甚少。目的：获得脂向分化过程中差异倍数明显的长非编码RNA,并进一步筛选在脂向分化过程中可能发挥重要作用的长非编码RNA进行验证。方法：取人腹部皮下脂肪,采用组织块培养法获取脂肪干细胞,传至第3代后进行成脂诱导分化,通过微阵列技术对脂向分化过程中0,5,12 d长非编码RNA及mRNA差异性表达量进行统计,并结合生物信息学报告筛选出呈现明显差异性表达的长非编码RNA,通过qRT-PCR进行验证。结果与结论：脂向分化过程中以差异倍数1.5（P＜0.05）为标准,上调长非编码RNA的数量5 d vs.0 d 748个,12 d vs.0 d 847个,12 d vs.5 d 593个;下调长非编码RNA的数量5 d vs.0 d 828个,12 d vs.0 d 1113个,12 d vs.5 d 750个;结合生物信息学分析结果,在与脂类代谢有关的28个长非编码RNA中根据诱导0,5,12 d 差异表达倍数较高且其靶基因可能是已知的与成脂相关的基因中,筛选出3个长非编码 RNA：AK304548、BP216319、DA852857。通过PCR验证结果显示AK304548、BP216319及其靶基因表达量呈现先下调后上调的趋势,与微阵列测序结果相符,预示其在脂向分化过程中起到调控作用。     

Towards diagnostic application of non-coding RNAs in neuroblastoma

Introduction: Neuroblastoma is a solid cancer of childhood, which is devastating upon recurrence. Markers for minimal residual disease and early detection of relapse are eagerly awaited to improve the outcome of affected patients. Several miRNAs have been identified as key regulators of neuroblastoma pathogenesis.

Areas covered: Here, we focus on miRNAs that have been linked to MYCN, a prominent oncogenic driver, and we review the hitherto known interactions between miRNAs and other important players in neuroblastoma.

Expert commentary: Existing diagnostic miRNA signatures remain to be established in clinical settings. Moreover, inhibition of individual oncogenic miRNAs or enhancement of tumor suppressive miRNA function could represent a new therapeutic approach in cancer treatment, including NB.     

Small non-coding RNAs in disease development and host-pathogen interactions

Non-coding RNAs (ncRNAs) play critical roles in all physiological processes. Many ncRNAs have also been implicated in a variety of pathological disorders, including cancer. This review provides an overview of the roles of small ncRNAs in infectious diseases and genetic disorders, including diseases of the CNS and various cancers. There is a focus on the consequences of microRNA (miRNA) de-regulation in human diseases, and recent progress in understanding other disease-related classes of ncRNAs, such as small nucleolar RNAs (snoRNAs), is presented. Finally, this review provides a brief perspective on new and powerful diagnostic strategies for human diseases that are based on ncRNA analysis, and presents novel potential approaches using ncRNAs as tools or targets for the treatment of such diseases.     

女性非吸烟肺癌相关lncRNAs 的生物信息学筛选及判断预后价值

目的筛选女性非吸烟肺癌患者中的差异表达长链非编码RNA(lncRNAs)。方法从Gene Expression Omnibus(GEO)数据库获得女性非吸烟肺癌患者的基因表达芯片GSE19804,利用GEO2R软件分析差异表达基因,利用DAVID数据库对差异基因进行重注释,获取差异表达的lncRNAs,利用Gene-E软件进一步分析和验证lncRNAs的表达情况。结果筛选出与女性非吸烟肺癌相关的差异表达lncRNAs 27个,与正常肺组织相比,11个表达上调,16个表达下调,差异具有统计学意义,其中高表达LINC00467的肺癌患者拥有较好的总生存期[HR(95%CI)=0.75(0.64~0.88),P0.01],低表达TINCR的肺癌患者拥有较差的总生存期[HR(95%CI)=1.31(1.11~1.55),P0.01]。结论利用生物信息学对已有芯片进行再分析可以快速筛选女性非吸烟肺癌患者相关lncRNAs。     

Role of non-coding RNAs in pathogenesis of gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GISTs) are considered the model solid malignancies of targeted therapy after the discovery of imatinib effectiveness against their tyrosine kinase inhibitors. Non-coding RNAs are molecules with no protein coding capacity that play crucial role to several biological steps of normal cell proliferation and differentiation. When the expression of these molecules found to be altered it seems that they affect the process of carcinogenesis in multiple ways, such as proliferation, apoptosis, differentiation, metastasis, and drug resistance. This review aims to provide an overview of the latest research papers and summarize the current evidence about the role of non-coding RNAs in pathogenesis of GISTs, including their potential clinical applications.     

Decoding the regulatory roles of non-coding RNAs in cellular metabolism and disease

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长链非编码RNA在肿瘤发生及发展中的作用机制

长链非编码RNA(lncRNA)是一类转录本长度＞200个核苷酸的非编码RNA(ncRNA),其在肿瘤的发生、发展中发挥重要作用.IncRNA具有多种生物学功能,可以通过诱饵分子、支架分子和向导分子等形式,在表观遗传学水平、转录水平及转录后水平,调控蛋白质编码基因的表达.lncRNA与肿瘤细胞生长和凋亡、侵袭和转移等生物学行为密切相关.进一步阐明IncRNA在肿瘤发生、发展过程中的作用机制,有望为研究者开发肿瘤诊断和治疗的新方法提供思路.笔者拟就lncRNA调控基因表达的作用机制,及其在肿瘤诊断及治疗中的作用进行综述.     

胃癌相关长链非编码RNA的作用及其意义

近年来,研究显示长链非编码RNA(long non-coding RNA,lncRNA)与包括胃癌在内的多种人类肿瘤的发生发展有关。一些lncRNA可能作为胃癌诊断的生物标志物或治疗靶点。因此,探索lncRNA的具体功能,不仅有助于更好地了解胃癌的发病机制,而且对胃癌患者的个体化治疗极其重要。现结合国内外相关研究报道,对近年来发现的一些与胃癌相关的lncRNA作简单综述。     

Functional interaction between long non-coding RNA and microRNA in rheumatoid arthritis

MicroRNA (miRNA) has received widespread attention for its role in several key cellular processes such as cell differentiation, cell proliferation, apoptosis, and autoimmune diseases. Although we now have a good understanding of miRNA expression and function, our knowledge regarding the molecular mechanism of long non-coding RNA (lncRNA) is still in its infancy. In this review, we will briefly introduce the definition and function of lncRNA and summarize the interactions between lncRNA and miRNA and their research progress in rheumatoid arthritis (RA). The expression of miR-16, miR-146a, miR-155, and miR-223 and the interactions between HOTAIR and miR138, ZFAS1 and miR-27a, and GAPLINC and miR-575 are representative examples that may augment the understanding of the pathogenesis of RA and help in the development of new biomarkers and target therapies.     

Exosomal non-coding RNAs: Emerging roles in bilateral communication between cancer cells and macrophages

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长链非编码RNA 91H在结直肠癌中的表达及功能研究

目的分析长链非编码RNA(lncRNA)91H在结直肠癌(CRC)患者中的表达情况,评估其与临床病理特征和预后的关系,并初步探讨其生物学功能。方法收集60例CRC手术患者的癌组织和癌旁组织,同时常规培养正常肠黏膜上皮细胞系FHC和CRC常规细胞系,用实时荧光定量RT-PCR检测lncRNA 91H在组织及细胞中的表达水平;并用CCK8法、流式细胞术和迁移侵袭实验评估lncRNA 91H干扰后对CRC细胞系生物学功能的影响。结果荧光定量RT-PCR检测结果显示91H在癌组织中的相对表达水平是癌旁组织的5.20±3.12倍,其在两组中的表达差异有统计学意义(t=4.30,P0.01);91H在4种CRC细胞系中的表达水平均明显高于FHC细胞系(F=99.22,P0.01);91H的高表达与肿瘤的远处转移(χ2=6.90,P0.01)和患者的不良预后相关(χ2=10.86,P0.01);多因素COX回归分析表明高表达的91H可以作为评估CRC预后的一个独立因子(HR=3.48,95%CI=1.35~8.96,P0.05)。体外实验结果表明,下调91H的表达可抑制CRC细胞的增殖、迁移侵袭,促进细胞凋亡(P均0.05)。结论 lncRNA 91H可促进CRC的发展,其可作为CRC预后判断的一个独立因子。     

Role of exosomal non-coding RNAs from tumor cells and tumor-associated macrophages in the tumor microenvironment

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