ceRNA与肿瘤

长链非编码RNA(LncRNA)、微小RNA(miRNA)、mRNA及假基因是竞争性内源RNA(ceRNA)理论的重要组成部分。LncRNA和miRNA都属于非编码RNA的范畴,不具备蛋白编码能力,不能翻译为蛋白质。LncRNA是一类转录本长度>200个核苷酸的RNA分子,可在表观遗传、转录或转录后调控等多种方式在生物体内发挥重要作用。MicroRNA长约22个核苷酸,可与靶mRNA 3UTR区互补结合,抑制靶mRNA的翻译或降解mRNA。mRNA具有蛋白编码能力,且大多数mRNA中分布大量的microRNA反应元件(MRE)。假基因拥有与编码基因高度同源的基因序列,与亲代编码基因相同或相似的MREs,但失去了编码蛋白质的能力。LncRNA,mRNA,假基因及miRNA可通过MREs进行相互作用,各类型RNA之间通过竞争MREs构成一个庞大的ceRNA调控网络,在肿瘤的发生发展中发挥重要作用。     

MALAT1、HOTAIR、NEAT1调控结直肠癌的研究进展

结直肠癌作为一种遗传性疾病,其发病机制涉及多个基因。长链非编码RNA(lncRNA)在肿瘤发生过程中起着重要的调节作用,对肿瘤的发展有重要影响。该文概述了lncRNA在结直肠癌中作为竞争性内源性RNA如何发挥其功能以及它们的表达是如何被调节,并重点介绍了以下lncRNA:HOTAIR、MALAT1、NEAT1在结直肠癌预后与肿瘤进展、侵袭、转移、细胞凋亡、放射抵抗等方面的作用机制,并阐明其作为治疗靶点的潜在作用。     

环状RNA调控肿瘤转移机制的研究进展

环状RNA(circular RNA,circRNA)是一类由前体mRNA经过不同剪切方式形成的环状非编码RNA.circRNA参与了许多病理过程,特别是在肿瘤的发生、发展及侵袭等过程中发挥着重要的调控作用.近年来,circRNA的功能研究越来越多,其功能所涉及的机制较为复杂,包括调控竞争性内源RNA(ceRNA)、RNA结合蛋白(RBP)、调控外泌体、编码小肽或蛋白等.笔者对circRNA调控肿瘤转移的相关机制及其研究进展综述如下.     

miRNA-125b在心脏疾病中的研究进展北大核心CSCD

microRNA（miRNA）是一类内源性非编码的单链RNA分子,长度约22个核苷酸,这些非编码小分子RNA与靶基因mRNA分子的3’端非编码区域（3’UTR）互补配对后,通过降低该mRNA分子的稳定性和抑制其翻译两种方式对靶基因进行转录后调控。自从1993年第一个miRNAlin-4被发现以来,20多年间已经有千余种miRNA陆续被发现,它们在炎症、发育、凋亡、细胞增殖和分化及肿瘤的发生等多种病理生理过程中发挥着重要作用。     

miR-146b在恶性肿瘤中的研究进展

微小RNA(microRNA,miRNA)是一类常见的非编码RNA,一般不被翻译为蛋白质,其主要作用是对基因表达进行调控.miRNA种类众多,作用机制十分复杂,其中miR-146b是一类多功能的miRNA,研究发现其在恶性胶质瘤、甲状腺癌、肺癌、肝细胞癌、胰腺癌、结直肠癌等诸多恶性肿瘤中的表达水平常常发生变化.本文就m...     

microRNA在结直肠癌研究中的新进展

microRNA（miRNA）是一类长约22~25个核苷酸的内源性非编码调控RNA,可参与细胞发育、增殖、分化和凋亡.miRNA具有癌基因和抑癌基因的作用,若干miRNA直接或间接参与结直肠癌的发生和发展,miRNA表达谱与结直肠癌的诊断、分期、进展和预后密切相关,为结直肠癌的早期发现和治疗起到一定的理论指导作用,将为结直肠癌的治疗提供新的策略和方法.     

长链非编码竞争性内源RNA在胃癌中的研究进展

长链非编码RNA(long non-coding RNA,LncRNA)是一类长度大于200个核苷酸并且能够在转录及转录后水平调节蛋白编码基因表达的非编码RNA,参与大量病理、生理过程。长链非编码RNA含有microRNA(miRNA)反应元件,可以和miRNA相互结合,影响目的基因的表达,此类lncRNA称为竞争性内源RNA(ceRNA),这种ceRNA参与胃癌的致病过程,为胃癌的致病机制提供了新的思路,通过阻断lncRNA与其相应位点的结合,也为胃癌的治疗提供新的靶点。     

长链非编码RNA在结直肠癌中的研究进展

结直肠癌的发生、发展是一个多步骤、多阶段、多基因参与的细胞遗传性疾病。长链非编码RNA(long non-coding RNA,lncRNA)是一类长度超过200 bp核苷酸,不具备蛋白质编码功能,但具有广泛的基因表达调控作用的非编码RNA分子。研究显示,lncRNA在多种肿瘤中异常表达,其在结直肠癌的发生、发展过程中具有重要的作用,可作为结直肠癌诊断和预后的特异性分子标志物以及有效的治疗靶点。该文就lncRNA在结直肠癌中的研究进展作一综述,以期为其临床研究结直肠癌的诊断和治疗提供依据。     

长链非编码RNA在结直肠癌中的研究进展

结直肠癌是常见的消化道恶性肿瘤,其发生涉及多步骤、多基因的相互作用等复杂过程。长链非编码RNA(long noncoding RNA,LncRNA)是一类长度超过200个核苷酸的无蛋白质编码功能却被证明具有广泛的基因表达调控作用的RNA分子。LncRNA在肿瘤发生、发展,侵袭及转移的过程中具有重要的作用。越来越多的研究揭示,大量LncRNA在结直肠癌中发生了异常表达(上调或下调),发挥着潜在的促癌和抑癌的作用。本文就在结直肠癌中表达上调或下调的LncRNA的最新研究进展作一综述。     

高血压相关的微小RNA研究进展

微小RNA(microRNA,miRNA)是在真核生物中发现的一类内源性具有调控功能的非编码RNA,其长度为19～30个核苷酸,由具70～90 nt的发夹结构单链RNA前体经Dicer酶加工后生成[1],通过识别靶向mRNA的3'非翻译区(3'untranslated region,3'-UTR)调节转录后基因沉默,可促进mRNA降解或抑制其转录以发挥在蛋白水平的调节功能[2]。miRNA参与了生命过程中的一系列重要进程,包括早期发育、细胞     

Potential roles of hsa_circ_000839 and hsa_circ_0005986 in breast cancer

BackgroundBreast cancer (BC) is one of the leading causes of death among women around the world. Circular RNAs (circRNAs) are a newly discovered group of non‐coding RNAs that their roles are being investigated in BC and other cancer types. In this study, we evaluated the association of hsa_circ_0005986 and hsa_circ_000839 in tumor and adjacent normal tissues of BC patients with their clinicopathological characteristics.Materials and methodsTotal RNA was extracted from tumors and adjacent non‐tumor tissues by the Trizol isolation reagent, and cDNA was synthesized using First Strand cDNA Synthesis Kit (Thermo Scientific). The expression level of hsa_circ_0005986 and hsa_circ_000839 was quantified using RT‐qPCR. Online in silico tools were used for identifying potentially important competing endogenous RNA (ceRNA) networks of these two circRNAs.ResultsThe expression level of hsa_circ_0005986 and hsa_circ_000839 was lower in the tumor as compared to adjacent tissues. The expression level of hsa_circ_0005986 in the patients who had used hair dye in the last 5 years was significantly lower. Moreover, a statistically significant negative correlation between body mass index (BMI) and hsa_circ_000839 expression was observed. In silico analysis of the ceRNA network of these circRNAs revealed mRNAs and miRNAs with crucial roles in BC.ConclusionDownregulation of hsa_circ_000839 and hsa_circ_0005986 in BC tumors suggests a tumor‐suppressive role for these circRNAs in BC, meriting the need for more experimentations to delineate the exact mechanism of their involvement in BC pathogenesis.     

竞争性内源性RNA在急性髓系白血病中的研究进展

急性髓系白血病 (acute myeloid leukemia, AML) 是多种因素引起的造血系统恶性疾病,具有很高的复发率及死亡率。非编码 RNA在 AML的发生发展过程中发挥着重要作用。竞争性内源性 RNA(competing endogenous RNA, ceRNA)观点指出,不同的非编码 RNA可通过作用于相同的 miRNA反应元件 (MRE)从而调控基因的表达。目前越来越多的研究表明,非编码 RNA作为 ceRNA在调控 AML的增殖、凋亡、侵袭和耐药等生物学过程中发挥关键作用。该文主要对 ceRNA在 AML生物学过程中的调控作用,以及治疗和预后中的临床意义作一综述。     

基于GEO 数据库筛选慢性胰腺炎恶变过程中关键miRNA 和ceRNA 网络构建

目的 筛选慢性胰腺炎（chronic pancreatitis, CP）进展到胰腺癌（pancreatic cancer, PC）过程中发挥潜在作用的 miRNA及其调控网络。方法 从 GEO数据库中下载芯片数据 GSE24279和 GSE25820,筛选出在 CP和 PC中差异表达的 miRNA（differential expression miRNA,DEM）。预测 DEM的靶基因和长链非编码 RNA（long non-coding RNA）,随后进行靶基因富集分析,构建蛋白互作网络（protein-protein interaction, PPI）并筛选出枢纽基因和具有特殊生物学功能的模块,通过综合分析 DEM,枢纽基因和 LncRNA的表达和预后,基于竞争性内源 RNA（competing endogenous RNAs, ceRNA）的理论,构建 miRNA的调控网络。结果 筛选出 16个 DEM,其靶基因参与共生过程,细胞器组织的正调控,细胞质的核周区域和双链 RNA结合。从 PPI网络中,筛选出 17个枢纽基因和 3个模块。综合分析后,将 hsa-miR-221-3p,hsa-miR-222-3p,hsa-miR-210-3p及 RNPS1,MGRN1作为 CP进展为 PC中关键节点。 41个 LncRNA结合关键 DEM,其中 MIAT,DANT2,TTN-AS1,PAXIP1-AS2和 LINC00473具有预后价值。综合以上结果,构建出包含 3个 DEM,2个基因和 5个 LncRNA的 ceRNA调控网络。结论 研究采用的整合分析方法有助于揭示 CP恶变的机制,构建的 LncRNA-miRNA-基因调控网络,为预测和治疗由 CP进展为 PC的患者提供了新的生物学靶点。     

Identification of lncRNA‐associated competing endogenous RNA networks for occurrence and prognosis of gastric carcinoma

BackgroundGastric cancer (GC) is one of the common digestive malignancies worldwide and causes a severe public health issue. So far, the underlying mechanisms of GC are largely unclear. Thus, we aim to identify the long non‐coding RNA (lncRNA)‐associated competing endogenous RNA (ceRNA) for GC.MethodsTCGA database was downloaded and used for the identification of differentially expressed (DE) lncRNAs, miRNAs, and mRNAs, respectively. Then, the ceRNA network was constructed via multiple online datasets and approaches. In addition, various in vitro assays were carried out to validate the effect of certain hub lncRNAs.ResultsWe constructed a ceRNA network, including 76 lncRNAs, 18 miRNAs, and 159 mRNAs, which involved multiple critical pathways. Next, univariate and multivariate analysis demonstrated 11 lncRNAs, including LINC02731, MIR99AHG, INHBA‐AS1, CCDC144NL‐AS1, VLDLR‐AS1, LIFR‐AS1, A2M‐AS1, LINC01537, and LINC00702, and were associated with OS, and nine of those lncRNAs were considered as hub lncRNAs involved in the sub‐ceRNA network. The in vitro assay indicated two lncRNAs, INHBA‐AS1 and CCDC144NL‐AS1, which were positively related to the GC aggressive features, including proliferation, invasion, and migration.ConclusionsWe identified nine hub lncRNAs and the associated ceRNA network related to the prognosis of GC, and then validated two out of them as promising oncogenes in GC.     

Retracted Article: Linc00472 suppresses breast cancer progression and enhances doxorubicin sensitivity through regulation of miR-141 and programmed cell death 4

The existence of drug resistance strikingly hampers the therapy of many malignancies, including breast cancer. Long non-coding RNAs (LncRNAs) have been reported to participate in the regulation of various biological processes associated with cancer progression. Whereas, the role of linc00472 in breast cancer pathogenesis and doxorubicin (ADR) resistance have not been well elucidated. In the present study, it is found that linc00472 expression was decreased in breast cancer tissues and cells. Moreover, higher linc00472 expression was positively associated with favorable disease status and prognosis for breast cancer patients. Functional analyses revealed that linc00472 overexpression suppressed proliferation and invasion, facilitated apoptosis and enhanced ADR sensitivity in breast cancer cells. Mechanistic studies discovered that linc00472 acted as a competing endogenous RNA (ceRNA) of miR-141 to sequester miR-141 from its target mRNA PDCD4 (programmed cell death 4). Furthermore, the inhibition effect of linc00472 on breast cancer cell progression and ADR resistance could be partly abrogated by miR-141 up-regulation or PDCD4 knockdown. In vivo assays also demonstrated that linc00472 hindered tumor growth by suppressing miR-141 expression and enhancing PDCD4 expression. In conclusion, linc00472 blocked breast cancer progression and induced ADR sensitivity through regulation of miR-141 and PDCD4, highlighting a potential therapeutic strategy for breast cancer patients.

Linc00472 expression was down-regulated in breast cancer tissues and cells, and was associated with the development and prognosis of breast cancer.     

RNA干扰技术在胚胎干细胞研究中的应用

RNA干扰是外源性或内源性双链RNA诱发的mRNA水平上的基因沉默机制,该技术在生物学研究中有着广泛的应用前景。最近将RNA干扰技术应用于胚胎干细胞的研究取得了显著效果,为胚胎干细胞的研究开辟了一条新途径。本文简述了RNA干扰技术的作用机制、在胚胎干细胞研究中的试验方法等最新进展。     

Fecal occult blood test screening for colorectal cancer

In summary, high-quality scientific studies indicate that the use of the FOBT for colorectal cancer screening has a number of important advantages. The test is capable of detecting most early colorectal cancers and many advanced adenomas. It has been shown in randomized, controlled trials to reduce substantially colorectal cancer mortality and incidence. The FOBT is feasible, widely available, and acceptable to most individuals. It has a low up-front cost and is highly cost-effective. Combining annual FOBT with periodic flexible sigmoidoscopy seems to be an especially effective screening option. Limitations of FOBT screening include its low sensitivity for polyps, especially smaller ones. Some of the trials report a relatively low sensitivity for detecting cancers located in the distal colon. The test has a relatively low specificity, so there are many false-positive screens; and for it to be most effective, repetitive screening is necessary. Balancing these advantages and disadvantages, the evidence-based screening guidelines have concluded that FOBT screening has a major role to play in colorectal cancer control and a program of annual FOBT plus flexible sigmoidoscopy every 5 years is a preferred option for screening the asymptomatic, average-risk population for colorectal cancer. Short of doing direct colonoscopy screening for the entire at-risk population, the FOBT currently is the best available method of identifying asymptomatic, average-risk people most likely to benefit from colonoscopy.     

干细胞相关因子在大肠癌组织及SW620细胞株的表达

背景：肿瘤细胞有多种干细胞标记的表达,深入研究其表达规律有助于揭示肿瘤发病机制、完善肿瘤干细胞理论。目的：检测大肠癌实体组织中干细胞相关分子标记CD133、CD166、Oct4、Sox2、C-myc、Klf4、Bmi-1与癌旁组织的表达差异,以及CD133免疫磁珠分选阳性与阴性SW620细胞中上述基因的表达差异。方法：选临床病理诊断清楚的29例大肠癌组织标本提取RNA,RT-PCR检测CD133、CD166、Oct4、Sox2、C-myc、Klf4、Bmi-1在大肠癌组织与癌旁对照组织中的表达。CD133免疫磁珠分选SW620,提取CD133细胞与CD133阴性细胞RNA,RT-PCR检测分选后上述基因的表达差异。结果与结论：29例标本均诊断为低、中分化腺癌或黏液腺癌,干细胞相关分子标记癌组织与癌旁组织表达灰度相对值癌组织表达均高于癌旁组织（P〈0.05）。RT-PCR检测分选后CD133＋细胞CD133,CD166,Oct4,Sox2,C-myc,Klf4,Bmi-1表达,结果均高于CD133-细胞。提示,CD133、CD166、Oct4、Sox2、C-myc、Klf4、Bmi-1相关干细胞标记可作为大肠癌肿瘤干细胞标记并有望用于诊断检测。     

Long noncoding RNA TUG1 upregulates VEGFA to enhance malignant behaviors in stomach adenocarcinoma by sponging miR‐29c‐3p

BackgroundLong noncoding RNA (lncRNA) TUG1 has been reported to display a pivotal role in the tumorigenesis and malignant progression of various types of cancers, including stomach adenocarcinoma (STAD). However, the contribution of aberrant expression of TUG1 and the mechanism by which it serves as a competing endogenous RNA (ceRNA) in STAD remains largely obscure.MethodsThe human STAD cell lines (MGC‐803 and AGS), human normal gastric epithelial cell line (GES‐1), human umbilical vein endothelial cells (HUVECs), and human embryonic kidney cells (HEK293T) were purchased and cultured to investigate the roles of TUG1 in STAD. Twenty BALB/c nude mice were purchased to establish a xenograft model to explore the roles of TUG1 in vivo.ResultsBioinformatics analysis revealed that TUG1 was upregulated in STAD, of which expression was negatively and positively correlated with miR‐29c‐3p and VEGFA, respectively. Functional analyses indicated that TUG1 functioned as an oncogene to promote malignant behaviors (proliferation, migration, and angiogenesis) of STAD cells; whereas miR‐29c‐3p exerted the opposite role. Mechanistically, the interaction between miR‐29c‐3p with TUG1 and VEGFA was demonstrated. It was observed that miR‐29c‐3p could reverse the TUG1‐induced promotion effect on cell proliferation, migration, and angiogenesis in STAD. Furthermore, TUG1 overexpression promoted STAD cell proliferation, metastasis, and angiogenesis, whereas VEGFA silence restored these effects, both in vitro and in vivo.ConclusionThis finding confirmed that lncRNA TUG1 acts as a ceRNA for miR‐29c‐3p to promote tumor progression and angiogenesis by upregulating VEGFA, indicating TUG1 as a therapeutic target in STAD management.