喉鳞癌中CircRNA、LncRNA、miRNA调控网络构建及功能研究

目的:探讨喉鳞状细胞癌（laryngeal squamous cell carcinoma，LSCC）中CircRNA、LncRNA、miRNA之间的共表达调控网络。方法:选取哈尔滨医科大学附属第二医院耳鼻咽喉头颈外科喉鳞状细胞癌患者标本，使用微阵列芯片技术对9对喉癌组织及其对应的癌旁非癌组织进行测序。筛选出差异表达的LncRNA、CircRNA、mRNA，通过TargetScan和miRanda算法对差异表达的RNA进行分析，构建出喉鳞状细胞癌的竞争内源性RNA（endogenous competitive RNA，ceRNA）网络。结果:发现8个LncRNA、6个CircRNA和13个mRNA以miR-107为中心形成共表达调控网络。6个LncRNA、3个CircRNA和20个mRNA以miR-19a-3p为中心形成共表达调控网络。结论:构建CircRNA/LncRNA、miRNA、mRNA之间的调控网络，为喉癌的后续治疗提供参考依据。     

环状RNA在胶质母细胞瘤中的研究进展

胶质母细胞瘤(glioblastoma,GBM)是一种致命的脑癌,约占美国恶性脑瘤的80%。目前有许多治疗方法可用于GBM,但是其预后水平低,中位生存时间不到15个月。因此,为了创造更有效的靶向治疗的新可能性,人们正在进行大量的研究,以了解GBM发展和进展的分子和遗传基础。CircRNA是普遍存在于各种生物体内,但最近才被发掘和证明,并逐步引起注重和深刻研讨的一种非编码RNA。环状RNA与癌症的发生息息相关。但对于胶质母细胞瘤来说,环状RNA的作用仍未知。本文以环状RNA在恶性胶质瘤(GBM)病理生物学中的作用,以及它们在恶性胶质瘤治疗中的潜在应用作一综述。     

环状RNA在肿瘤中的研究进展

摘 要：环状RNA（circRNA）是一类不同于线性RNAs,可形成共价闭锁环结构,在哺乳动物体内具有巨大基因调控功能的非编码RNAs,其主要来源于外显子或内含子,经索尾插接或套索内含子方式产生,具有数量巨大,进化保守、在细胞质中稳定性高等特点,具有microRNA分子海绵、结合RNA相关蛋白形成RNA-蛋白质复合物和基因转录调控等作用。CircRNA可与肿瘤相关的miRNA形成circRNA-miRNA轴参与肿瘤相关信号通路的调控。全文从circRNA的种类、成环机制、功能及其在肿瘤中的作用及最新进展等方面作一综述。     

环状RNA CircHIPK3通过miR-379调控IGF1表达促进非小细胞肺癌细胞系NCI-H1299与NCI-H2170的细胞增殖

背景与目的 已有的研究证明:环状RNA是一类在哺乳动物中普遍存在的具有稳定闭合环状结构的内源性RNA分子.环状RNA circHIPK3(circular RNA HIPK3,circHIPK3)在肝细胞癌(hepatocellular carcino-ma,HCC)中表达水平较高,促进肝癌细胞生长.但是其在非小细胞肺癌(non-small cell lung cancer,NSCLC)中的作用及其调控机制尚无文献报道.本研究拟探讨环状RNA circHIPK3对NSCLC细胞系NCI-H1299和NCI-H2170细胞增殖的影响,并进一步研究其调控的分子机制.方法 Real-time PCR法检测circHIPK3在NSCLC各细胞系中的表达水平.CCK-8实验和克隆形成实验检测过量表达和干扰circHIPK3对细胞增殖的影响.双荧光素酶报告基因实验分别检验miR-379与circHIPK3及miR-379与IGF1 mRNA的结合情况.Western blot和ELISA检测细胞内外的IGF1蛋白表达水平.结果 环状RNA circHIPK3在6株NSCLC细胞株中均有表达,其中H1299表达最低,H2170表达最高,通过转染过表达的circHIPK3可显著促进NCI-H1299细胞增殖,干扰circHIPK3可显著抑制NCI-H2170细胞增殖.miR-379可与circHIPK3及IGF1 mRNA直接结合.过表达circHIPK3导致IGF1表达量上调,干扰circHIPK3能够下调IGF1表达水平,转入miR-379 mimics恢复了circHIPK3稳转细胞株IGF1表达水平的上调及细胞增殖表型.结论 环状RNA circHIPK3在NSCLC细胞系NCI-H1299及NCI-H2170中可通过miR-379调控IGF1表达促进细胞增殖,环状RNA circHIPK3可能成为非小细胞肺癌治疗的新靶点.     

环状RNA在肿瘤转移中的研究进展

环状 RAN（circular RAN，circRNA）是一种广泛存在于哺乳动物体内具有共价闭合环状结构的非编码 RAN。CircRNA具有高度的稳定性和保守性，成为近年来表观遗传学领域研究的热点。肿瘤转移是导致肿瘤患者死亡最主要的原因，提高对肿瘤转移机制的理解至关重要。随着对 circRNA 研究的逐渐深入，其在肿瘤转移中的作用及相关机制逐渐被挖掘。CircRNA通过影响上皮间质转化（epithelial-mesenchymal transition，EMT）、肿瘤免疫逃逸、肿瘤血管生成、DNA甲基化修饰和外泌体功能等方面在肿瘤转移中发挥重要作用，为肿瘤转移的机制研究提供了新的思路。因此，circRNA有望成为新的肿瘤标志物和治疗靶点。本文就circRNA的结构特征及其在肿瘤转移中的作用作一综述。     

GEO数据库分析环状RNA在乳腺癌组织中的表达

目的采用生物信息学方法探究环状RNA在乳腺癌侵袭转移中的作用。方法从GEO数据库中检索并下载乳腺癌组织的芯片数据,利用R软件对4对Luminal A型乳腺癌组织和4对三阴性乳腺癌组织进行差异分析,然后利用miRanda 软件和 RNAhybrid 软件对差异表达的环状RNA和miRNAs之间的相互作用进行预测。通过TCGA数据库分析环状RNA的亲本基因在乳腺癌组织中的表达。结果通过差异分析,发现共有27个环状RNA异常表达,其中6个环状RNA上调,21个环状RNA下调;通过软件预测构建了环状RNA／miRNAs相互作用网络;通过基因表达分析,hsa_circ_0000965、hsa_circ_0000523、hsa_circ_0044234、hsa_circ_0058451和hsa_circ_0091994可能正向调控其亲本基因的表达。结论在三阴性乳腺癌组织中的异常表达环状RNA将可能成为乳腺癌转移治疗的新靶点。     

circRNA在肿瘤中的研究进展

环状RNA（circRNA）是3'-端与5'-端共价结合生成的闭合环状RNA分子,在肿瘤中可作为原癌基因和抑癌基因,通过海绵吸附miRNA、结合RNA结合蛋白、结合酶与相应底物、调控转录以及翻译多肽或蛋白等机制发挥重要的生物作用。circRNA通过circRNA-miRNA-mRNA轴影响多种肿瘤的发生与发展,具有肿瘤诊断和预后标志物的潜力,成为继miRNA及长链非编码RNA（lncRNA）之后又一个研究热点。     

环状RNA在肿瘤中的研究进展

摘 要：环状RNA(circular RNA,circRNA )是一类由mRNA 3′及5′末端首尾相连形成的无蛋白编码功能的RNA分子,研究发现其可通过调节肿瘤相关基因转录水平及转录后水平来促进肿瘤的发病,并与肿瘤的转移、预后等显著相关。该文通过总结环状RNA在肿瘤中的研究进展,发现其可通过与miRNA的海绵作用以及调控肿瘤信号通路因子的方式在肿瘤的发生发展中发挥相应作用。环状RNA在肿瘤发病中作用的具体分子机制研究,可为肿瘤的预防、早期诊断及精准治疗提供一种全新的理论支持。     

环状RNA的m6A甲基化修饰及其在肿瘤中的研究进展

环状RNA是一类广泛存在于生物体中的非编码RNA,具有较高的分子结构稳定性、高度保守性和表达特异性。N⁶-甲基腺苷(N⁶-methyladenosine, m⁶A)是真核生物RNA中常见的修饰。大量的证据表明环状RNA和m⁶A RNA甲基化修饰在肿瘤的发生和发展中起着至关重要的作用。本文叙述了环状RNA和m⁶A RNA甲基化修饰的概念以及二者与肿瘤的联系,汇总了肿瘤相关的具有m⁶A RNA甲基化修饰的环状RNA,并讨论了其在临床领域的应用前景,以期为肿瘤的早期诊断、临床治疗及预后预测方面提供新思路。     

环状RNA与肿瘤研究进展

目的 环状RNA(circular RNAs,circRNAs)是一种不同于线性RNA的新型RNA,其广泛存在于各种生物细胞中.本研究总结了环状RNA的生物起源、作用机制以及其在肿瘤发生发展中的作用.方法 应用中国知网和PubMed中英文数据库,以“circRNAs和肿瘤”等为关键词,检索2014-2016年的相关文献.纳入标准:(1) circRNAs的生物学合成;(2)circRNAs的作用机制;(3) circRNAs在肿瘤发生发展中的作用.根据纳入标准,符合分析的文献35篇.结果 circRNA是一类新型非编码RNA,共价闭合环路所形成的环状结构是它的特征.这类具有组织特异性的转录本主要来自宿主基因的外显子或内含子序列.尽管已提出circRNAs多种生物起源模式,但是对circRNAs的了解还只是冰山一角.circRNAs的表达与多种痰病有关,并且可能作为该疾病新型诊断或预后预测的生物标志物.circRNAs可以调节与肿瘤相关的miRNAs的表达,这种circRNA-miR-NA-mRNA轴可以调控与癌症相关通路,既可促进也可以桔抗肿瘤的发生发展.结论 深入研究环状RNA在肿瘤的发生发展中所起的作用,有望在肿瘤的诊断和靶向治疗以及顸后判断方面提供新的思路.     

Circular RNAs 0064286 and 0000475: Potential Diagnostic Biomarkers in Hepatocellular Carcinoma

Objective: Hepatocellular carcinoma (HCC) is considered the highest recorded malignancy in Egypt. The shortage of appropriate biomarkers for early detection often results in the late diagnosis of the HCC. Circular RNAs (CircRNAs) are presented as long stranded non-coding RNA that combine covalently to make a sealed circular form which make them very stable. CircRNAs are known to have interpretative role in cancer development and metastasis. Aim: To examine the dysregulation of two new CircRNAs obtained from Circbase database (hsa_circ_0064286 and hsa_circ_0000475) in the serum of HCC patients as predictable diagnostic biomarkers of HCC and their correlation with some liver biochemical parameters. Methods: Sixty clinically diagnosed HCC Egyptian patients and 25 healthy volunteers were enrolled in the study. Expression levels of the selected CircRNAs was evaluated in subjects’ serum. Moreover, correlation with liver biochemical parameters, sensitivity, and specificity of studied CircRNAs were estimated. Results: Both circular RNAs were significantly down regulated in HCC patients, which was negatively correlated with ALP, ALT, AST, AFP, and bilirubin levels. Circ_0064286 showed more sensitivity and specificity (88.3% and 96%, respectively). Conclusion: As far as we know, this is the first study that shed light on the expression levels of both circRNAs in Egyptian HCC patients. They may serve as potential biomarkers for HCC diagnosis. Moreover, those circRNAs draw attention as therapeutic targets for HCC through targeting their sponge miRNAs.     

circRNAs in drug resistance of breast cancer

Breast cancer (BC) is the most common heterogeneous disease in women and one of the leading causes of cancer-related death. Surgery, chemotherapy, radiotherapy, hormone, and targeted therapy are the gold standards for BC treatment. One of the significant challenges during the treatment of BC represents resistance to chemotherapeutics, resistance that severely limits the use and effectiveness of the drugs used for BC treatment. Therefore, it is essential to develop new strategies to improve therapeutic efficacy. Circular RNAs (circRNAs) are a large group of non-coding RNAs that covalently form closed circular loops by joining their 5′, and 3′; ends. Accumulating evidence suggests that circRNAs have a vital role in cancer development, progression, and BC resistance to chemotherapy. The purpose of this review is to discuss the biological properties of circRNAs, and how circRNAs induce resistance to conventional therapeutic anti-cancer drugs used in BC treatment, by emphasizing and summarizing the potential roles of circRNAs in mechanisms of drug resistance, such as drug efflux, apoptosis dysfunction, autophagy, and DNA damage repair. CircRNAs are associated with drug resistance via ATP-binding cassette (ABC) efflux transporters, while some others by inhibition of cell apoptosis, thus leading to resistance to tamoxifen in BC cells. In contrast, others are involved in the promotion of BC cells chemoresistance by doxorubicininduced autophagy. CircRNAs may have clinical significance in regulating or overcoming BC drug resistance and may give directions towards a novel approach to personalized BC treatment. CircRNAs may significantly contribute to the identification of new therapeutic targets for the prevention of BC chemoresistance.     

环状RNA在肿瘤疾病中的研究进展

环状RNA是一种新型RNA,在生物体中具有microRNA“海绵”、RNA结合蛋白及核转录调节等功能。在肿瘤疾病中,环状RNA主要以miRNA“海绵”的形式发挥调控作用,促进或抑制肿瘤的发生和发展。此外,环状RNA还可以作为肿瘤早期诊断、预后评估的生物标记物,也可作为抗肿瘤治疗的靶标,具有潜在的临床诊断治疗价值。本文就环状RNA在肿瘤疾病中的作用机制及临床应用进行综述。      

The biogenesis,function and clinical significance of circular RNAs in breast cancer

Circular RNAs (circRNAs) are noncoding RNAs that form covalently closed loop structures. CircRNAs are dysregulated in cancer and play key roles in tumorigenesis...     

Circulating circRNAs as Potential Biomarkers for Cancers

Cancers are diseases with a high mortality rate worldwide. In order to better diagnose and improve the survival rate, many studies have been conducted. In recent years, the role of non-coding RNAs in cancers has been confirmed, and circular RNAs (circRNAs) have attracted much attention. CircRNAs are involved in the occurrence and development of cancers with high stability. Experiments have shown that they can exist stably in peripheral blood. Therefore, the expression of circulating circRNAs can be detected to help diagnose cancers and reflect tumor progression. In this review, we summarized the role of circulating circRNAs in cancers and discussed their potential as biomarkers.     

环状RNAs在肿瘤防治中的研究进展

环状RNAs(circRNAs)是一类具有单链封闭结构的非编码RNA。目前circRNAs得到越来越多的重视,研究已经确定了circRNAs与各种肿瘤的相关性。其主要是通过作为微小RNA(miRNA)的“分子海绵”对细胞生物学过程进行调节。目前发现,circRNA在人体多种疾病的发展过程中都存在差异表达,这种差异在肿瘤性疾病中更加明显。大多数circRNAs在各种肿瘤中均存在失调,其中一些在肿瘤的发生、发展中起重要作用。因此,在circRNA中寻找肿瘤诊断和治疗的靶点,有望为肿瘤的靶向治疗提供新的方向。本文综述了circRNAs在肿瘤研究中的最新进展,并展望了circRNAs在肿瘤防治中的新作用以及未来的挑战。