Wnt/β-catenin信号通路相关长链非编码RNA在肿瘤进展中的功能与机制

长链非编码RNA（lncRNA）是一类长度大于200 nt、且不编码的RNA。lncRNA 已被证明与人类疾病紧密相关，尤其是肿瘤发生发展。研究表明，肿瘤中一些异常表达的lncRNA 可以通过不同的信号通路，如Wnt/β-catenin 信号通路，促进肿瘤进展过程。在不同肿瘤组织中具有特异性表达特征的lncRNA与Wnt/β-catenin 信号通路之间的相互作用显示出其作为新的生物标志物和治疗靶点的潜能。本文就Wnt/β-catenin 信号通路相关lncRNA 通过调控Wnt/β-catenin 信号转导，影响不同肿瘤类型发生发展的作用进行综述。本文结果或可为临床肿瘤诊断和治疗提供新的思路。     

人类癌症中长链非编码RNA与miRNA相互作用的研究进展

人类基因组中大部分为非编码区,转录产生非编码RNA（ncRNA）。这些ncRNA可以在表观遗传学水平及转录后水平调控癌基因和抑癌基因的表达,影响肿瘤的发生和发展,是肿瘤诊断、治疗及预后判断的潜在靶标。微小RNA（miRNA） 和长链非编码RNA（lncRNA） 是ncRNA的两个重要分类。其中,lncRNA通过多种机制在不同水平进行基因表达调控,发挥其生物学功能,这些机制包括基因印迹、染色质重塑、细胞周期调控、选择性剪接、mRNA降解和翻译调控等。近年来,miRNA和lncRNA在癌症发生发展中相互作用的分子机制引起了人们的注意。本文主要就这两者在癌症发生发展过程中的相互作用机制及研究方法进行综述。     

肿瘤相关巨噬细胞与长链非编码RNA在肿瘤发展中的研究进展

肿瘤相关巨噬细胞是肿瘤微环境重要组成部分，极化亚型影响肿瘤进展过程。长链非编码RNA(long non-coding RNA，lncRNA)不编码蛋白质，但是同样参与生物学过程，异常表达的lncRNA影响生理和病理进程，尤其对肿瘤发展有重要调控作用。癌症中一些异常表达的lncRNA直接或者间接影响巨噬细胞极化亚型调控肿瘤发展进程，lncRNA和巨噬细胞之间调节机制尚未清楚。lncRNA同肿瘤相关巨噬细胞可作为肿瘤潜在靶点和治疗中间物。本文将对在肿瘤中相互作用的肿瘤相关巨噬细胞与长链非编码RNA调控肿瘤进展过程进行综述。      

lncRNA、microRNA在卵巢癌中的研究进展及相互作用关系

人类基因组中大部分为非编码区,转录产生非编码 RNA(ncRNA) 。这些ncRNA可以在表观遗传水平、转录水平及转录后水平调控基因的表达,进而影响肿瘤的发生和发展,是肿瘤诊断、治疗及预后判断的潜在靶标。微小RNA(microRNA ,miRNA) 和长链非编码RNA(long non-coding RNA,lncRNA) 是 ncRNA 的两个重要分类。越来越多的研究表明lncRNA、microRNA 参与生物体的各种生理及病理过程,其中恶性肿瘤的相关研究最多。卵巢癌是妇科常见的恶性肿瘤疾病,早期诊断困难、预后差。MicroRNA和 lncRNA 在卵巢癌的发生发展中的研究进展及相互作用关系近年来引起了人们的关注。本文就这两者在卵巢癌的发生发展过程中的相互作用机制及研究进展作一综述。     

lncRNA SNHGs在前列腺癌发生发展中的研究进展

前列腺癌已成为威胁老年男性健康的全球性“杀手”,其发生发展机制以及治疗方法是当前的研究重点。近年来,基因转录或转录后调控机制被证明在前列腺癌进展中发挥关键的作用,其中长链非编码RNA(long non-coding RNA,lncRNA)扮演着重要的角色。lncRNA SNHGs与前列腺癌关系密切,其不仅影响肿瘤生物学特性,在前列腺癌细胞凋亡、自噬、侵袭、细胞增殖等方面发挥至关重要的作用,而且与肿瘤预后相关。其作用机制与ceRNA学说、Wnt/β-catenin、PI3K/AKT/mTOR等信号通路有关。本文就lncRNA SNHGs在前列腺癌发生发展中的作用做一综述,希望能为前列腺癌的诊治提供新思路。     

lncRNA在食管鳞癌转移中的作用及机制

食管鳞状细胞癌(ESCC)具有高度侵袭性和转移性,早期易发生转移,预后差,是世界范围内常见的癌症之一。长链非编码RNA(long non-coding RNA,lncRNA)作为转录调控因子,可以调控多种基因组过程和细胞过程,如细胞增殖、迁移和侵袭等。lncRNA也被证明参与调节与肿瘤转移相关的信号通路。已有大量研究试图揭示lncRNA在食管癌发生和转移中的重要作用。本文着重强调lncRNA在表观遗传学、基因表达水平以及作为竞争性内源性RNA途径的作用,综述lncRNA在ESCC转移中的研究进展,对于 ESCC患者的预后监测和靶向治疗具有重要意义。     

双同源盒假基因9在肿瘤发生发展中的作用及机制

长链非编码RNA（long non-coding RNA,lncRNA）是由RNA聚合酶II转录的长度大于200个核苷酸并且不编码蛋白的RNA，不仅可以调控人体的生长发育过程而且在肿瘤的发生发展中也发挥重要作用。双同源盒假基因9（double homeobox A pseudogene 9,DUXAP9）作为一种在诸多肿瘤中表达异常上调的lncRNA，可以通过内源性竞争RNA、招募蛋白、介导上皮间质转化以及激活信号通路等方式来调控肿瘤的恶性生物学行为。对DUXAP9的促癌作用机制进行深入研究有助于相关肿瘤的早期诊断和靶向治疗。本文就DUXAP9在肿瘤发生发展中的作用及机制作一综述。     

lncRNA在消化系统肿瘤中的研究进展

长链非编码RNA (long noncoding RNA, lncRNA) 是一组长度大于200个核苷酸、缺少特异完整的开放阅读框、无蛋白质编码功能的RNA, 在总非编码RNA (ncRNA) 中占有相当大的比例。因其数量、种类、功能状况均不明确, 被称为基因组中的“暗物质”。本研究对其参与肿瘤的发生发展进行了探讨, 发现随着新一代基因测序技术的应用, lncRNA介导了信号转导通路、调控细胞周期并诱导细胞凋亡。本文结合国内外最新报道, 对lncRNA在消化系统肿瘤中的研究进展做一综述, 以期为消化系统肿瘤的基因诊断和治疗提供新的思路。      

肿瘤中长链非编码RNA GIHCG的表达及作用研究进展

摘 要：长链非编码RNA（long non-coding RNA，lncRNA）是一类长度大于200个核苷酸且基本不能编码蛋白质的RNA分子，在诸多肿瘤中表达异常的lncRNA能够参与调控肿瘤的发生与发展。长链非编码RNA GIHCG（gradual increased during hepatocarcinogenesis）是近年在肝细胞癌研究中新发现的一种lncRNA，其异常高表达与多种恶性肿瘤患者预后密切相关。GIHCG可通过内源竞争性吸附miRNA、调节细胞周期以及激活多种信号通路来调控肿瘤的恶性生物学行为，对GIHCG作用的研究有助于相关肿瘤的诊断、治疗及评估预后。全文就肿瘤中长链非编码RNA GIHCG的表达及作用的研究进展进行综述。     

TGF-β 诱导的长链非编码RNA 在肿瘤中的研究进展

转化生长因子β（transforming growth factor- β ,TGF-β）信号通路参与调控细胞增殖、分化、凋亡等,以细胞或环境依赖的方式发挥肿瘤抑制或肿瘤促进作用,成为肿瘤发生发展过程中的一把双刃剑。长链非编码RNA （longnon-codingRNA ,lncRNA）不编码蛋白,但参与多种信号通路及生物学功能的调控,可诱导血管生成,在多种肿瘤的增殖、侵袭和转移过程中起到重要作用,发挥类似癌基因或抑癌基因的作用。TGF-β 可诱导产生一些具有重要调控功能的lncRNA,从而形成复杂的交联调控网络。本文将对目前报道的能被TGF-β 诱导,且机制与作用相对清楚的lncRNA 进行综述。      

Integrating developmental signals: a Hippo in the (path)way

The Hippo pathway, a signaling cascade that controls cell cycle progression, apoptosis and cell differentiation, has emerged as a fundamental regulator of many physiological and pathological processes. Recent studies have revealed a complex network of interactions directing Hippo pathway activity, and have connected this pathway with other key signaling pathways. Such crosstalk has uncovered novel roles for Hippo signaling, including regulation of TGFβ/SMAD and WNT/β-catenin pathways. This review highlights some of the recent findings in the Hippo field with an emphasis on how the Hippo pathway is integrated with other pathways to mediate diverse processes.     

Hippo‐YAP signaling pathway: A new paradigm for cancer therapy

In the past decades, the Hippo signaling pathway has been delineated and shown to play multiple roles in the control of organ size in both Drosophila and mammals. In mammals, the Hippo pathway is a kinase cascade leading from Mst1/2 to YAP and its paralog TAZ. Several studies have demonstrated that YAP/TAZ is a candidate oncogene and that other members of the Hippo pathway are tumor suppressive genes. The dysregulation of the Hippo pathway has been observed in a variety of cancers. This review chronicles the recent progress in elucidating the function of Hippo signaling in tumorigenesis and provide a rich source of potential targets for cancer therapy.     

Hippo-YAP signaling in digestive system tumors

The Hippo pathway is an evolutionally conserved pathway and plays an important role in regulating tissue hemostasis and organ size control. Deregulation of the Hippo pathway is implicated in various human digestive system tumors. The past two decades have witnessed the discovery and elucidation of key signaling components and molecular mechanisms of the Hippo pathway. Among these, the signaling transducers YAP/TAZ are in the center of this complex network to sense and respond to extracellular cues such as cell contact, matrix stiffness and growth factors. In this review, we summarize the biological and clinical significance of Hippo-YAP signaling in the digestive system tumors, and explore the novel therapeutic strategies for targeting Hippo-YAP signaling.     

Willin/FRMD6 expression activates the Hippo signaling pathway kinases in mammals and antagonizes oncogenic YAP

The Salvador/Warts/Hippo (Hippo) signaling pathway defines a novel signaling cascade regulating cell contact inhibition, organ size control, cell growth, proliferation, apoptosis and cancer development in mammals. The Drosophila melanogaster protein Expanded acts in the Hippo signaling pathway to control organ size. Previously, willin/FRMD6 has been proposed as the human orthologue of Expanded. Willin lacks C-terminal sequences that are present in Expanded and, to date, little is known about the functional role of willin in mammalian cells. When willin is expressed in D. melanogaster epithelial tissues, it has the same subcellular localization as Expanded, but cannot rescue growth defects associated with expanded deficiency. However, we show that ectopic willin expression causes an increase in phosphorylation of the core Hippo signaling pathway components MST1/2, LATS1 and YAP, an effect that can be antagonized by ezrin. In MCF10A cells, loss of willin expression displays epithelial-to-mesenchymal transition features and willin overexpression antagonizes YAP activity via the N-terminal FERM domain of willin. Therefore, in mammalian cells willin influences Hippo signaling activity by activating the core Hippo pathway kinase cassette.     

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.     

Non-coding RNAs in DNA damage response

Genome-wide studies have revealed that human and other mammalian genomes are pervasively transcribed and produce thousands of regulatory non-protein-coding RNAs (ncRNAs), including miRNAs, siRNAs, piRNAs and long non-coding RNAs (lncRNAs). Emerging evidences suggest that these ncRNAs also play a pivotal role in genome integrity and stability via the regulation of DNA damage response (DDR). In this review, we discuss the recent finding on the interplay of ncRNAs with the canonical DDR signaling pathway, with a particular emphasis on miRNAs and lncRNAs. While the expression of ncRNAs is regulated in the DDR, the DDR is also subjected to regulation by those DNA damage-responsive ncRNAs. In addition, the roles of those Dicer- and Drosha-dependent small RNAs produced in the vicinity of double-strand breaks sites are also described.     

Hippo通路和相关长链非编码RNA（LncRNA）与肿瘤关系的研究进展

Hippo信号通路是近年来在果蝇体内发现的一条新的细胞信号通路,主要功能包括保持细胞增殖凋亡、调控器官体积,其调控异常将导致肿瘤的发生。LncRNA（long non-coding RNA,LncRNA）是一类长度大于200个核苷酸的非编码RNA,缺少特异开放阅读框,不具备蛋白质编码功能。研究显示,LncRNA与肿瘤的发生、发展、转移密切相关。本文就Hippo信号通路和相关LncRNA与肿瘤关系的研究进展做一综述。     

长链非编码RNA调控癌症细胞信号通路的研究进展

迄今为止,研究人员应用功能基因组学方法发现了多种类型的长链非编码RNA。长链非编码RNA能够调控基因的表达,并且在包括癌症等疾病发生发展过程中起着重要的作用。长链非编码RNA调控基因的表达过程有多种机制参与,例如对转录、翻译、蛋白质修饰及RNA-蛋白复合体形成或者蛋白-蛋白复合体形成等过程的调控。本文主要探讨长链非编码RNA调控肿瘤细胞信号通路的研究进展。     

Hippo信号通路在肺癌中的研究进展

肺癌是全世界范围内肿瘤相关性死亡的首要原因,每年死亡人数超过100万人,占全球癌症死亡人数的五分之一.虽然目前在手术、放化疗、靶向治疗、免疫治疗肺癌方面取得了一定进展,但患者的预后仍不理想.因此,亟待寻找评价预后的分子标志物和肺癌的治疗新靶点,为肺癌患者提供生存获益的有效方法.近年来,Hippo信号通路逐渐成为国内外肿瘤研究领域中新兴且热门的研究方向.Hippo信号通路激活时,其核心组件MST/MOB、LATS 1/2等能抑制转录的共激活剂YAP/TAZ的转录,二者被磷酸化并滞留在细胞浆中,从而抑制肺癌的发生发展.因此Hippo信号通路在临床应用中的潜在价值也越来越受关注.本篇文章总结了Hippo信号通路核心组成元件及上下游调控因子在肺癌形成进展过程中的重要作用和分子机制,并对Hippo信号通路的研究前景进行展望.