Long noncoding RNA profiles identify five distinct molecular subtypes of colorectal cancer with clinical relevance

Colorectal cancer (CRC) is a heterogeneous disease in terms of clinical behavior and response to therapy. Increasing evidence suggests that long noncoding RNAs (lncRNAs) are frequently aberrantly expressed in cancers, and some of them have been implicated in CRC biogenesis and prognosis. Using an lncRNA-mining approach, we constructed lncRNAs expression profiles in approximately 888 CRC samples. By applying unsupervised consensus clustering to LncRNA expression profiles, we identified five distinct molecular subtypes of CRC with different biological pathways and phenotypically distinct in their clinical outcome in both univariate and multivariate analysis. The prognostic significance of the lncRNA-based classifier was confirmed in independent patient cohorts. Further analysis revealed that most of the signature lncRNAs positively correlated with somatic copy number alterations (SCNAs). This lncRNAs-based classification schema thus provides a molecular classification applicable to individual tumors that has implications to influence treatment decisions.     

Comprehensive analysis of long non-coding RNAs in human breast cancer clinical subtypes

Accumulating evidence highlights the potential role of long non-coding RNAs (lncRNAs) as biomarkers and therapeutic targets in solid tumors. However, the role of lncRNA expression in human breast cancer biology, prognosis and molecular classification remains unknown. Herein, we established the lncRNA profile of 658 infiltrating ductal carcinomas of the breast from The Cancer Genome Atlas project. We found lncRNA expression to correlate with the gene expression and chromatin landscape of human mammary epithelial cells (non-transformed) and the breast cancer cell line MCF-7. Unsupervised consensus clustering of lncRNA revealed four subgroups that displayed different prognoses. Gene set enrichment analysis for cis- and trans-acting lncRNAs showed enrichment for breast cancer signatures driven by master regulators of breast carcinogenesis. Interestingly, the lncRNA HOTAIR was significantly overexpressed in the HER2-enriched subgroup, while the lncRNA HOTAIRM1 was significantly overexpressed in the basal-like subgroup. Estrogen receptor (ESR1) expression was associated with distinct lncRNA networks in lncRNA clusters III and IV. Importantly, almost two thirds of the lncRNAs were marked by enhancer chromatin modifications (i.e., H3K27ac), suggesting that expressed lncRNA in breast cancer drives carcinogenesis through increased activity of neighboring genes. In summary, our study depicts the first lncRNA subtype classification in breast cancer and provides the framework for future studies to assess the interplay between lncRNAs and the breast cancer epigenome.     

小细胞肺癌组织中lncRNA表达谱的差异

目的：观察长链非编码RNA（ lncRNA）在未发生转移的小细胞肺癌和发生转移的小细胞肺癌组织中表达的差异。方法：利用高通量lncRNA芯片技术分别检测3例未发生转移的小细胞肺癌组织和3例发生转移的小细胞肺癌组织中lncRNA表达谱的变异,经对原始数据进行预处理达到均一化后,筛选出差异表达的lncRNA,进行聚类分析。结果：将lncRNA表达在发生转移的小细胞肺癌组织中与未发生转移的小细胞肺癌组织中的变化倍数在2倍以上并有显著差异（ P＜0.05）的lncRNA,确定为差异性表达的lncRNA。其中在3例发生远处转移的患者肺癌组织中变化均在2倍以上的共842条,占所有lncRNA的12.1％。其中,2倍以上表达上调的共440条,2倍以上表达降低的共402条;5倍以上表达升高的共31条;5倍以上表达降低的共65条。结论：发生转移的小细胞肺癌组织与未发生转移的小细胞肺癌组织比较,lncRNA表达谱发生显著变化。提示差异性表达的lncRNAs参与了小细胞肺癌侵袭和转移的恶性表型。     

甲状腺肿瘤相关性非编码RNA研究进展

非编码RNA（non-codingRNA,ncRNA）是指除mRNA、tRNA和rRNA以外,不编码蛋白质的RNA。近年研究显示,ncRNA在细菌、真菌和哺乳动物等多种生物体的活动中可作为癌基因或抑癌基因,对肿瘤的发生、发展发挥调控作用。此外,ncRNA有希望成为肿瘤诊断的新型标志物。本文介绍了一些与甲状腺肿瘤相关的ncRNA最新研究进展,并着重讨论微RNA（miRNA）及长链非编码RNA（IncRNA）在甲状腺肿瘤发生、转移中的作用。     

我国动脉粥样硬化基础研究几个热点领域的新进展

动脉粥样硬化(As)是一种好发于大、中等动脉的由多因素导致的复杂的血管壁慢性病变。其病理特征包括脂质蓄积、平滑肌细胞迁移入内膜并增殖、炎性细胞浸润、胶原沉积、斑块形成等。越来越多的证据表明,NLRP3炎症小体、细胞焦亡、外泌体、肠道菌群、外周血管脂肪组织、非编码RNA等与As的发生发展紧密联系在一起,并成为目前的研究热点。对上述因素在As发生发展中的作用的深入研究将有助于进一步理解As的发生机制及寻找新的有效治疗途径和生物标记物。文章对近两年来中国学者围绕上述方面进行的As基础研究进展作一综述。     

lncRNA MALAT1靶向miR-150对口腔鳞癌细胞增殖和凋亡的影响及分子机制

目的:研究MALAT1对口腔鳞癌细胞SCC-25增殖、凋亡的影响，并探讨其机制。方法:运用qRT-PCR检测人口腔鳞癌细胞SCC-25、人永生化口腔上皮细胞HIOEC中MALAT1和miR-150的mRNA表达；将si-con组（转染si-con）、si-MALAT1组（转染si-MALAT1）、miR-150组（转染miR-150 mimics）、miR-con组（转染miR-con）、si-MALAT1+anti-miR-con组（si-MALAT1和anti-miR-con共转染）、si-MALAT1+anti-miR-150组（si-MALAT1和anti-miR-150共转染），均以脂质体法转染至SCC-25细胞；MTT法检测各组细胞的增殖；流式细胞术检测各组细胞的凋亡；双荧光素酶报告基因检测实验检测各组细胞的荧光活性。结果:与人永生化口腔上皮HIOEC细胞（Normal组）相比，口腔鳞癌SCC-25细胞（Tumor组）中MALAT1表达显著上调，miR-150显著下调（P＜0.05）；敲减MALAT1、过表达miR-150均可抑制SCC-25细胞增殖，促进凋亡；MALAT1靶向miR-150。抑制miR-150逆转了敲减MALAT1对口腔鳞癌细胞的增殖抑制和凋亡促进作用。结论:MALAT1可促进口腔鳞癌细胞增殖并抑制凋亡，其机制可能与靶向miR-150有关，可为口腔鳞癌的治疗提供新靶点。