长链非编码RNA作为潜在药物靶点的研究进展

随着生命科学的不断发展,2012年DNA元件百科全书（ENCODE）项目进一步丰富了人类基因组功能元件的相关信息。该项目 发现人类基因组超过80%的序列会被转录,其中大部分转录本是非编码RNA（ncRNA）。目前,在这些非编码RNA中,小RNA的研究 相对深入,而长链非编码RNA（lncRNA）的研究相对较少。越来越多研究表明,很多lncRNA参与到人类重大疾病的发生、发展过程之 中,并且一些动物实验证实lncRNA可作为药物靶点。因此,从lncRNA角度筛选新的药物靶点也越来越受到研究者的关注。重点总结了 lncRNA的生物学功能及作为潜在药物靶点的研究进展。     

循环长链非编码RNA作为生物标志物在肿瘤分子诊断中的应用

长链非编码RNA(Long noncoding RNA,lncRNA)被发现广泛参与基因表达、表观遗传调控和X染色体失活等重要生命过程,还与肿瘤发生和发展密切相关。lncRNA可能以微泡、外泌体或蛋白质复合物形式进入人体循环系统中,形成循环lncRNA稳定而广泛存在于血液、尿液等体液中。文中简要回顾了近来关于循环lncRNA的来源,以及作为生物标志物的检测方法,着重总结分析了循环lncRNA作为潜在肿瘤生物标志物在肺癌、乳腺癌、胃癌、肝癌、结直肠癌和前列腺癌等常见恶性肿瘤中的早期诊断价值。与传统生物标志物相比,循环lncRNA具有作为新型生物标志物的独特优势和临床应用价值。     

SNHG16 Silencing Inhibits Neuroblastoma Progression by Downregulating HOXA7 via Sponging miR-128-3p

Neurochemical Research - Neuroblastoma (NB) is a common intracranial solid tumor with high mortality. Small nucleolar RNA host gene 16 (SNHG16), one of the long noncoding RNAs (lncRNAs), has been...     

Long noncoding RNA AANCR modulates innate antiviral responses by blocking miR-210-dependent MITA downregulation in teleost fish,Miichthys miiuy

Viral infection induces the initiation of antiviral effectors and cytokines which are critical mediators of innate antiviral responses.The critical molecular determinants are responsible for triggering an appropriate immune response. Long noncoding RNAs(lncRNAs) have emerged as new gene modulators involved in various biological processes, while how lncRNAs operate in lower vertebrates are still unknown. Here, we discover a long noncoding RNA, termed antiviral-associated long noncoding RNA(AANCR), as a novel regulator for innate antiviral responses in teleost fish. The results indicate that fish MITA plays an essential role in host antiviral responses and inhibition of Siniperca chuatsi rhabdovirus(SCRV) production. miR-210 reduces MITA expression and suppress MITA-mediated antiviral responses, which may help viruses evade host antiviral responses. Further,AANCR functions as a competing endogenous RNA(ceRNA) for miR-210 to control protein abundance of MITA, thereby inhibiting SCRV replication and promoting antiviral responses. Our data not only shed new light on understanding the function role of lncRNA in biological processes in teleost fish, but confirmed the hypothesis that ceRNA networks exist widely in vertebrates.     

Long noncoding RNAs biomarker-based cancer assessment

Cancer diagnosis have mainly relied on the incorporation of molecular biomarkers as part of routine diagnostic tool. The molecular alteration ranges from those involving DNA, RNA, noncoding RNAs (microRNAs and long noncoding RNAs [lncRNAs]) and proteins. lncRNAs are recently discovered noncoding endogenous RNAs that critically regulates the development, invasion, and metastasis of cancer cells. They are dysregulated in different types of malignancies and have the potential to serve as diagnostic markers for cancer. The expression of noncoding RNAs is altered following many diseases, and besides, some of them can be secreted from the cells into the circulation following the apoptotic and necrotic cell death. These secreted noncoding RNAs are known as cell free RNA. These RNAs can be secreted from the cell through the apoptotic body, extracellular vesicles including microvesicle and exosome, and bind to proteins. Since, lncRNAs display high organ and cell specificity, can be found in the blood, urine, tumor tissue, or other tissues or bodily fluids of some patients with cancer, this review summarizes the most significant and up-to-date findings of research on lncRNAs involvement in different cancers, focusing on the potential of cancer-related lncRNAs as biomarkers for diagnosis, prognosis, and therapy.     

DNA methylation and gene expression profiles characterize epigenetic regulation of lncRNAs in colon adenocarcinoma

The long noncoding RNAs (lncRNAs) are associated with tumorigenesis and progression of cancer. While DNA methylation is a common epigenetic regulator of gene expression, the methylation of lncRNAs was rarely studied. To address this gap, we integrated DNA methylation and RNA-seq data to characterize the landscape of lncRNA methylation in colon adenocarcinoma (COAD). We collected and analyzed the lncRNA expression and methylation data from The Cancer Genome Atlas and Cancer Cell Line Encyclopedia to identify the epigenetically regulated lncRNAs. We further investigated the biological and clinical relevance of the identified lncRNAs via bioinformatics analysis. We identified 20 epigenetically upregulated lncRNAs in COAD, including several well-studied lncRNAs whose methylation regulation were poorly investigated, such as PVT1 and UCA1. We also revealed several novel tumor-associated lncRNAs in COAD, including GATA2-As1 and CYTOR. Next, we explored their biology function using gene set enrichment analysis and competitive endogenous RNA analysis. We characterized the methylation landscape of lncRNA in COAD and identified 20 epigenetically upregulated lncRNAs. Our findings will shed new light on the epigenetic regulation of lncRNA expression by DNA methylation.     

Genomic maps of long noncoding RNA occupancy reveal principles of RNA-chromatin interactions

Long noncoding RNAs (lncRNAs) are key regulators of chromatin state, yet the nature and sites of RNA-chromatin interaction are mostly unknown. Here we introduce Chromatin Isolation by RNA Purification (ChIRP), where tiling oligonucleotides retrieve specific lncRNAs with bound protein and DNA sequences, which are enumerated by deep sequencing. ChIRP-seq of three lncRNAs reveal that RNA occupancy sites in the genome are focal, sequence-specific, and numerous. Drosophila roX2 RNA occupies male X-linked gene bodies with increasing tendency toward the 3' end, peaking at CES sites. Human telomerase RNA TERC occupies telomeres and Wnt pathway genes. HOTAIR lncRNA preferentially occupies a GA-rich DNA motif to nucleate broad domains of Polycomb occupancy and histone H3 lysine 27 trimethylation. HOTAIR occupancy occurs independently of EZH2, suggesting the order of RNA guidance of Polycomb occupancy. ChIRP-seq is generally applicable to illuminate the intersection of RNA and chromatin with newfound precision genome wide.