特异长链非编码RNA在鼻咽癌中的表达及其意义

目的 分析长链非编码RNA（long non-coding RNA, lncRNA）在鼻咽癌与慢性鼻咽炎组织中表达水平的变化,寻找可能与鼻咽癌发生发展相关的特异lncRNA。方法 采用lncRNA芯片技术分析lncRNA和mRNA在鼻咽癌与慢性鼻咽炎组织的表达谱,筛选差异表达的lncRNA和mRNA,进一步研究使用了聚类分析、GO分析、pathway分析等生物信息学技术。结果 差异表达的lncRNA（2倍以上变化且P＜0.05）共856条,其中上调的共 425条,下调的共431条;差异表达的mRNA共767条,其中上调的共426条,下调的共341条。利用聚类分析方法将差异表达的lncRNA分成3类：增强子型lncRNA、HOX 基因簇、基因间lncRNA。GO分析将mRNA分成3类：生物学过程类、细胞组分类、分子功能类。Pathway分析显示mRNA共参与28条信号通路,其中参与细胞因子-细胞因子受体相互作用信号通路的上调差异表达的mRNA的富集度最高。结论 与慢性鼻咽炎相比,lncRNA在鼻咽癌组织的表达水平明显改变,提示差异表达的lncRNA可能与鼻咽癌的发生发展有关。     

HOTAIR: an oncogenic long non-coding RNA in different cancers

Long non-coding RNAs (lncRNAs) refer to a group of RNAs that are usually more than 200 nucleotides and are not involved in protein generation. Instead, lncRNAs are involved in different regulatory processes, such as regulation of gene expression. Different lncRNAs exist throughout the genome. LncRNAs are also known for their roles in different human diseases such as cancer. HOTAIR is an lncRNA that plays a role as an oncogenic molecule in different cancer cells, such as breast, gastric, colorectal, and cervical cancer cells. Therefore, HOTAIR expression level is a potential biomarker for diagnostic and therapeutic purposes in several cancers. This RNA takes part in epigenetic regulation of genes and plays an important role in different cellular pathways by interacting with Polycomb Repressive Complex 2 (PRC2). In this review, we describe the molecular function and regulation of HOTAIR and its role in different types of cancers.KEYWORDS : HOTAIR, long non-coding RNA (lncRNA), epigenetic, cancer     

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。     

新疆哈萨克族食管鳞癌与长链非编码RNA表达的关系

目的:对新疆哈萨克族食管鳞癌组织及癌旁组织长链非编码RNA(lnc RNA)表达谱进行分析,并探讨其与食管癌发生和发展的关系。方法:采用基因芯片技术,对4组食管鳞癌及其癌旁组织中差异表达的lnc RNA进行筛选,通过lnc RNA-m RNA共表达网络对靶基因进行预测,利用GO和KEGG数据库进行富集分析和通路分析,明确lnc RNA的功能。结果:癌组织和癌旁组织之间差异表达的lnc RNA共318个,与癌旁组织比较,癌组织中193个lnc RNA表达上调,125个lnc RNA表达下调(P<0.01)。富集分析表明共有5个GO类别,其中细胞成分有3个,生物过程有1个,分子功能有1个,均通过反式调控方式调控靶基因。通路分析表明这些差异表达的基因可能参与轴突导向信号通路和ECM受体相互作用途径信号通路。结论:新疆哈萨克族食管鳞癌组织中lnc RNA的表达水平与癌旁组织有明显差异,差异表达的lnc RNA可能参与食管癌的复杂调控网络,并与肿瘤发生和发展有一定的关系。     

新疆哈萨克族食管鳞癌与长链非编码RNA表达的关系

目的：对新疆哈萨克族食管鳞癌组织及癌旁组织长链非编码RNA（lncRNA）表达谱进行分析，并探讨其与食管癌发生和发展的关系。方法：采用基因芯片技术，对4组食管鳞癌及其癌旁组织中差异表达的lncRNA进行筛选，通过lncRNA-mRNA共表达网络对靶基因进行预测，利用GO和KEGG数据库进行富集分析和通路分析，明确lncRNA的功能。结果：癌组织和癌旁组织之间差异表达的lncRNA共318个，与癌旁组织比较，癌组织中193个lncRNA表达上调，125个lncRNA表达下调（P < 0.01）。富集分析表明共有5个GO类别，其中细胞成分有3个，生物过程有1个，分子功能有1个，均通过反式调控方式调控靶基因。通路分析表明这些差异表达的基因可能参与轴突导向信号通路和ECM受体相互作用途径信号通路。结论：新疆哈萨克族食管鳞癌组织中lncRNA的表达水平与癌旁组织有明显差异，差异表达的lncRNA可能参与食管癌的复杂调控网络，并与肿瘤发生和发展有一定的关系。     

长链非编码RNA MAFG-AS1在骨肉瘤中的表达及功能

目的:探讨及分析骨肉瘤中差异表达长链非编码RNA（long non-coding RNA,lncRNA）的表达谱及功能。方法:本课题前期通过5对组织（骨肉瘤组织和瘤旁组织）进行高通量转录组学测序筛选出差异表达的lncRNAs,并筛选出上调变化的前5位lncRNAs,通过荧光定量PCR在骨肉瘤细胞系内检测lncRNA MAFG-AS1的差异表达,并通过小干扰RNA技术干扰其表达,CCK-8法检测敲低lncRNA后细胞增殖是否发生变化,Western-blotting检测下游蛋白变化。结果:高通量数据分词浅析显示,共有376个lncRNAs在骨肉瘤组织中差异表达,其中206个上调,170个下调,并筛选出上调变化的前5位lncRNAs。荧光定量PCR显示lncRNA MAFG-AS1在骨肉瘤细胞内高表达。CCK-8法结果显示该lncRNA MAFG-AS1具有影响骨肉瘤细胞增殖的作用,且下游蛋白RRM2表达发生变化。结论:骨肉瘤组织中存在明显的lncRNAs差异性表达。且lncRNA MAFG-AS1在骨肉瘤发生和发展中发挥中重要的作用。     

长链非编码RNA在肿瘤耐药中的研究进展

化疗药物耐药性仍然是目前肿瘤有效化疗的主要障碍。尽管肿瘤耐药机制受到了广泛的探索,但至今尚未被完全阐明。长链非编码RNA是近年来的研究热点,参与了基因组功能的许多方面包括基因转录、剪接、表观遗传学以及细胞周期、细胞分化、发育和多能性等过程。在肿瘤耐药中lncRNA可能通过促进DNA修复、改变药物代谢和细胞膜流出、调节细胞凋亡率和影响上皮细胞-间充质转化等过程,调节化疗敏感性。同时,lncRNA表达谱与肿瘤耐药的演变有密切关系。因此,发现新的lncRNA在肿瘤耐药中的机制对于制定新的治疗策略以克服耐药性具有积极意义。     

Microarray Analysis of Long Non-coding RNA Expression Profile Associated with 5-Fluorouracil-Based Chemoradiation Resistance in Colorectal Cancer Cells

Background: Preoperative 5-fluorouracil (5-FU)-based chemoradiotherapy is a standard treatment for locallyadvanced colorectal cancer (CRC). However, CRC cells often develop chemoradiation resistance (CRR). Recentstudies have shown that long non-coding RNA (lncRNA) plays critical roles in a myriad of biological processesand human diseases, as well as chemotherapy resistance. Since the roles of lncRNAs in 5-FU-based CRR inhuman CRC cells remain unknown, they were investigated in this study. Materials and Methods: A 5-FU-basedconcurrent CRR cell model was established using human CRC cell line HCT116. Microarray expression profilingof lncRNAs and mRNAs was undertaken in parental HCT116 and 5-FU-based CRR cell lines. Results: In total,2,662 differentially expressed lncRNAs and 2,398 mRNAs were identified in 5-FU-based CRR HCT116 cellswhen compared with those in parental HCT116. Moreover, 6 lncRNAs and 6 mRNAs found to be differentiallyexpressed were validated by quantitative real time PCR (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis for the differentially expressed mRNAs indicated involvement of many, such as Jak-STAT, PI3K-Akt and NF-kappa B signaling pathways. To better understand the molecular basis of 5-FU-basedCRR in CRC cells, correlated expression networks were constructed based on 8 intergenic lncRNAs and theirnearby coding genes. Conclusions: Changes in lncRNA expression are involved in 5-FU-based CRR in CRCcells. These findings may provide novel insight for the prognosis and prediction of response to therapy in CRCpatients.     

长链非编码RNA在胶质母细胞瘤中异常表达研究

背景与目的：近来研究表明,长链非编码RNA在胶质瘤的发生与发展中发挥重要作用。本研究旨在通过基因芯片分析lncRNAs在胶质母细胞瘤（GBM）和正常脑组织中的表达概况,比较lncRNA差异表达与组织之间的表达谱差异。方法：应用基因芯片技术检测lncRNAs在GBM和正常脑组织的表达谱差异．并筛选出差异表达lncRNA进行分析。结果：lncRNA芯片的数据：原发性胶质母细胞瘤与正常脑组织中LncRNA表达上调3倍基因2032个,LncRNA表达下调3倍基因2036个（P〈0．01）。其中21个lncRNAs上调30倍以上．7个lncRNAs下调超过30倍（P〈0．01）。结论：利用lncRNA基因芯片较大规模地对胶质瘤中的lncRNAs差异表达进行探讨．对lncRNA在其中的功能及潜在的基因治疗功能具有十分重要的意义：差异表达的lncRNAs包括一些抑癌及促癌lncRNA,其在胶质母细胞瘤的发展中扮演重要的角色．通过它们的目标基因在GBM的复发和恶性进展中发挥作用．     

Transcriptome profiling of lncRNA and co-expression networks in esophageal squamous cell carcinoma by RNA sequencing

Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of cancer. To identify novel targets for further study in esophageal squamous cell carcinoma (ESCC), we performed a genome-wide analysis of lncRNA expression in 12 ESCC tumor and normal tissues. Publicly available RNA-seq data were downloaded from the NCBI, GEO, and Co-LncRNA databases, and lncRNA and messenger RNA (mRNA) expression profiles were analyzed. In total, 127 lncRNAs were found to be differentially expressed, with a greater than fourfold change in ESCC tumor tissues compared with normal tissues. Among these lncRNAs, 98 were upregulated and 29 downregulated. Moreover, 1469 network nodes and 1720 connection edges between 119 lncRNAs and 1350 coding genes were integrated into the lncRNA and mRNA co-expression network. Bioinformatic analysis using GO terms revealed that these dysregulated lncRNAs are associated with developmental processes, proteinaceous extracellular matrix, and protein binding activity, with ECM-receptor interaction and the PI3K-Akt signaling pathway enrichment. Lastly, qRT-PCR results verified two significantly upregulated lncRNAs and three significantly downregulated lncRNAs in 50 pairs of ESCC tissues and adjacent normal tissues. These results reveal the landscape of ESCC-associated lncRNAs and co-expression networks, providing important insight regarding the lncRNAs involved in ESCC.     

长链非编码RNA FOXD2-AS1在骨肉瘤细胞中的表达及功能

目的:探讨长链非编码RNA FOXD2-AS1在骨肉瘤细胞中的表达谱及其功能。方法:前期对5对组织（骨肉瘤组织和正常组织）进行转录组学测序筛选出差异表达的lncRNAs,并筛选出上调变化的具有研究意义的前五位lncRNAs。通过荧光定量PCR进一步在骨肉瘤组织及正常组织内验证lncRNA FOXD2-AS1差异表达这一趋势,利用siRNA技术干扰其表达,筛选出干扰lncRNA FOXD2-AS1效率最高的两条siRNAs,CCK-8法及流式细胞术检测敲减lncRNA后细胞增殖及凋亡是否发生变化。结果:转录组学测序筛选出上调变化明显的前5位lncRNAs,并进一步通过实时荧光定量PCR显示lncRNA FOXD2-AS1在骨肉瘤组织内高表达,CCK-8法及流式细胞术结果显示该高表达的lncRNA FOXD2-AS1促进骨肉瘤细胞增殖,且抑制骨肉瘤细胞的凋亡。结论:骨肉瘤与正常组织相比,存在明显的高表达lncRNAs,且高表达的lncRNA FOXD2-AS1促进骨肉瘤的增殖并抑制其凋亡,在骨肉瘤进展中发挥至关重要的作用。     

lncRNA 的生物标记作用及 MEG3在肿瘤中的研究进展

长链非编码 RNA（lncRNA）是 RNA 分子学的一个新类型,由于转录长度超过200个核苷酸缺乏蛋白编码潜能而得名。一些 lncRNA 在特殊类型的癌症中具有高度特异的表达使其成为潜在的诊断工具,另一些 lncRNA 与肿瘤生长和患者生存期不同的病理生理特点有相关性,使其成为指示预后的生物标记物。众多 lncRNA 之一的母系表达基因3（MEG3）是一种印记基因,包含12个亚型基因,编码与肿瘤发生相关的lncRNA。MEG3通过调节 p53和促血管再生等发挥作用,提示 MEG3及其亚型可作为一个新型的 lncRNA 肿瘤抑制因子。近年来,有关 lncRNA 与肿瘤的相关性已成为研究的热点,本文就 lncRNA 生物标记作用和MEG3及其亚型与肿瘤疾病的研究进展作一综述。     

Construction and analysis of lncRNA-lncRNA synergistic networks to reveal clinically relevant lncRNAs in cancer

Long non-coding RNAs (lncRNAs) play key roles in diverse biological processes. Moreover, the development and progression of cancer often involves the combined actions of several lncRNAs. Here we propose a multi-step method for constructing lncRNA-lncRNA functional synergistic networks (LFSNs) through co-regulation of functional modules having three features: common coexpressed genes of lncRNA pairs, enrichment in the same functional category and close proximity within protein interaction networks. Applied to three cancers, we constructed cancer-specific LFSNs and found that they exhibit a scale free and modular architecture. In addition, cancer-associated lncRNAs tend to be hubs and are enriched within modules. Although there is little synergistic pairing of lncRNAs across cancers, lncRNA pairs involved in the same cancer hallmarks by regulating same or different biological processes. Finally, we identify prognostic biomarkers within cancer lncRNA expression datasets using modules derived from LFSNs. In summary, this proof-of-principle study indicates synergistic lncRNA pairs can be identified through integrative analysis of genome-wide expression data sets and functional information.