lncRNA MEG3在肿瘤发生发展中的功能作用与机制研究进展

人母系表达基因(maternally expressed gene 3,MEG3)属于长链非编码RNA（long-chain non coding RNA,lncRNA）,在人类许多正常组织中均有表达。目前MEG3在多种人类癌症组织为低表达,且其基因启动子呈现高甲基化状态,进而影响肿瘤细胞的增殖、迁移、侵袭、凋亡等方面,是肿瘤发生发展的抑制因子。lncRNA MEG3对肿瘤的分子调控作用,揭示其有望成为治疗的新靶点。本文综述了MEG3在各肿瘤中的功能作用与机制,讨论了MEG3在各肿瘤中的意义及存在的问题。但MEG3在肿瘤中的具体作用机制仍未阐明,需做进一步研究。     

小细胞肺癌组织中lncRNA MEG3的表达及其与预后关系的研究

目的 探讨长链非编码RNA MEG3（lncRNA MEG3）在小细胞肺癌（SCLC）组织中的表达及其与预后的关系。方法 收集2012年1月至2015年12月间于我院就诊的SCLC组织标本92例,采用实时荧光定量PCR（QPCR）法检测lncRNA MEG3在92例SCLC组织、40例癌旁组织及50例正常肺组织标本中的表达,分析其表达与临床病理特征和预后的关系。结果 与癌旁组织（4.082±0.86）和正常肺组织（4.209±0.82）比较,lncRNA MEG3在92例SCLC组织中的表达（2.071±0.97）明显降低,差异有统计学意义（P＜0.001）。lncRNA MEG3表达与年龄、性别无关,与分期、远处转移及生存状态有关。lncRNA MEG3低表达者（＜2.071）的中位无进展生存期为8个月,较高表达者（≥2.071）的21个月短,差异有统计学意义（P＜0.001）;高表达者的中位总生存期为32个月,较低表达组的21个月长,差异有统计学意义（P＜0.001）。Cox比例风险模型分析显示,lncRNA MEG3表达、远处转移和分期均为影响SCLC总生存期的独立因素。结论 lncRNA MEG3参与调节SCLC的发生、发展,可作为潜在的评估SCLC预后的分子标志物。     

长链非编码RNA MEG3 在胃癌中的表达及其与预后的关系

目的:研究长链非编码RNA （long non-coding RNA ,lncRNA）母系表达基因3（maternally expressed gene3,MEG3）在胃癌组织中的表达及其与预后的关系,并进一步探讨MEG3 与凋亡相关蛋白P 53、鼠双微基因2（murine double minute 2,MDM2）的相关性。方法:收集2012年9 月至2013年6 月青岛大学附属青岛市市立医院55例行手术治疗的胃癌切除标本（包括癌组织及对应的远端正常组织）,实时荧光定量PCR（qRT-PCR）检测胃癌组织中MEG3 的表达,并分析其与临床病理参数的关系;应用免疫蛋白印迹法（Western blot）检测胃癌中P 53、MDM2 蛋白的表达水平,并分析其与MEG3 的相关性。结果:lncRNAMEG 3 在胃癌组织的相对表达水平（7.98± 0.19）低于所对应的正常组织（9.47± 0.18,P < 0.05）;在胃癌组织（r =-0.627,P < 0.001）及远端正常组织（r =-0.807 ,P < 0.001）中,P 53与MDM2 的表达呈负相关;P 53与MEG3 的表达呈正相关（r = 0.591,P < 0.05）,MDM2 与MEG3 的表达呈负相关（r =-0.346,P < 0.05）;MEG3 高表达者较低表达者中位生存期明显延长。结论:MEG3 在胃癌发生发展过程中起抑癌基因的作用;MEG3 与P 53、MDM2 在胃癌发生发展的生物学机制上有重要联系;检测MEG3 的表达水平对胃癌预后有潜在价值。      

长链非编码 RNA MEG3在肿瘤研究中的进展

近来研究发现,长链非编码 RNA MEG3在多种肿瘤组织（非小细胞肺癌、结直肠癌、乳腺癌等）中呈低表达,表现为抑癌基因的功能,在肿瘤的发生、发展、预后及化疗耐药中具有重要作用,有望成为肿瘤诊断及治疗的一种新型生物标记物。本文结合国内外最新报道对 MEG3在肿瘤研究中的进展作一综述。     

膀胱癌中长链非编码RNA研究进展

膀胱癌是泌尿系统最常见肿瘤之一,具有高复发性和预后差的特点。近年来发现长链非编码RNA（long non-coding RNA,lncRNA）在膀胱癌的基因表达调控中起着重要的作用,且lncRNA的表达异常与膀胱癌的发生和发展密切相关,其既可以作为促癌基因,也可作为抑癌基因。lncRNA可能成为膀胱癌诊断及预后的重要生物标记物,本文对近年来膀胱癌中的lncRNA研究进展作一综述。     

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。     

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。     

微小RNA相关调控通路与肿瘤发生发展

 研究表明,微小RNA（miRNA）在多数肿瘤中存在异常表达。miRNA相关调控通路,包括miRNA与蛋白编码基因及miRNA与长链非编码RNA（lncRNA）间的相互调控,与肿瘤的发生发展密切相关。miRNA有望成为临床肿瘤治疗的新靶点。     

长链非编码 RNA MEG3在非小细胞肺癌中的表达与功能

目的：探讨长链非编码 RNA MEG3在非小细胞肺癌中的表达情况及其分子机制。方法：采用 qRT -PCR 方法检测肺癌组织中 MEG3的相对表达量,分析其与临床病理资料的相关性。将 MEG3转染到肺癌A549细胞后,应用 qRT - PCR 检测 A549细胞中 MEG3的表达;MTT 检测细胞转染后肿瘤细胞增殖的变化;并用 Western blot 检测转染后细胞中凋亡相关蛋白（BCL -2和 BCL - XL）表达。结果：肺癌组织中 MEG3的相对表达水平显著低于正常肺组织（P <0.05）。各肺癌细胞株中 MEG3的表达水平均低于肺上皮细胞株（P <0.05）。MEG3的表达水平与肿瘤大小、临床分期以及淋巴结转移之间有显著相关性（P <0.05）。MEG3转染A549细胞48h 和72h 后,A549细胞的增殖率明显低于空白对照组和阴性对照组（P <0.05）。其 BCL - XL 蛋白表达水平相较于空白对照组和阴性对照组表达明显下调（P <0.05）。结论：MEG3在 NSCLC 肿瘤组织中表达下调,可能部分通过下调 BCL - XL 的表达而抑制肺癌细胞的增殖。     

LncRNA：非小细胞肺癌诊断治疗的新策略

肺癌是全球最常见的恶性肿瘤,是全世界癌症相关死亡的主要原因.LncRNA是指一类至少包含200个核苷酸且不具有编码蛋白质功能的RNA.许多lncRNA都具有促进或抑制NSCLC发展及恶化的功能.由于其调节基因表达方面的基础作用,连同其在肿瘤生成的生物学机制,它们是一类有前途的组织或血液生物标志物.本文我们强调lncRNA在NSCLC的新兴作用,并讨论其作为诊断和预后的生物标志物及治疗靶点的潜在临床应用.     

microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer

The human genome is replete with long non-coding RNAs (lncRNA), many of which are transcribed and likely to have a functional role. Microarray analysis of >23,000 lncRNAs revealed downregulation of 712 (~3%) lncRNA in malignant hepatocytes, among which maternally expressed gene 3 (MEG3) was downregulated by 210-fold relative to expression in non-malignant hepatocytes. MEG3 expression was markedly reduced in four human hepatocellular cancer (HCC) cell lines compared with normal hepatocytes by real-time PCR. RNA in situ hybridization showed intense cytoplasmic expression of MEG3 in non-neoplastic liver with absent or very weak expression in HCC tissues. Enforced expression of MEG3 in HCC cells significantly decreased both anchorage-dependent and -independent cell growth, and induced apoptosis. MEG3 promoter hypermethylation was identified by methylation-specific PCR and MEG3 expression was increased with inhibition of methylation with either 5-Aza-2-Deoxycytidine, or siRNA to DNA Methyltransferase (DNMT) 1 and 3b in HCC cells. MiRNA-dependent regulation of MEG3 expression was studied by evaluating the involvement of miR-29, which can modulate DNMT 1 and 3. Overexpression of mir-29a increased expression of MEG3. GTL2, the murine homolog of MEG3, was reduced in liver tissues from hepatocyte-specific miR-29a/b1 knock-out mice compared with wild-type controls. These data show that methylation-dependent tissue-specific regulation of the lncRNA MEG3 by miR-29a may contribute to HCC growth and highlight the inter-relationship between two classes of non-coding RNA, miRNAs and lncRNAs, and epigenetic regulation of gene expression.     

Long noncoding RNA MEG3 is downregulated in cervical cancer and affects cell proliferation and apoptosis by regulating miR-21

Recent research has found that long noncoding RNAs (lncRNAs) were involved in various human cancers. However, the role of these lncRNAs in cervical cancer remains unexplored. Therefore, we aimed to investigate the biological function of maternally expressed gene 3 (MEG3), a cancer-related lncRNA, and its underlying mechanism in cervical cancer. In this study, MEG3 expression of 108 patients’ cervical cancer tissues and adjacent normal tissues was detected by quantitative real-time PCR analysis (qRT-PCR), and the functional effect of MEG3 was determined in vitro assays. We observed that MEG3 was downregulated in cervical cancer tissues, compared to the adjacent normal tissues, and was negatively related with FIGO stages, tumor size, lymphatic metastasis, HR-HPV infection and the expression of homo sapiens microRNA-21 (miR-21). Furthermore, we focused on the function and molecular mechanism of MEG3, finding that overexpression of MEG3 reduced the level of miR-21-5p expression, causing inhibition of proliferation and increased apoptosis in cervical cancer cells. In summary, our findings indicate that MEG3 function as a tumor suppressor by regulating miR-21-5p, resulting in the inhibition of tumor growth in cervical cancer. As a result, this study improves our understanding of the function of MEG3 in cervical cancer and will help to provide new potential target sites for cervical cancer treatment.     

Long non-coding RNAs are involved in alternative splicing and promote cancer progression

Alternative splicing (AS) is a key process in which precursor RNAs produce different mature RNAs, and the disorder of AS is a key factor in promoting cancer development. Compared with coding RNA, studies on the functions of long non-coding RNAs (lncRNAs) are far from enough. In fact, lncRNA is an important participant and regulator in the process of AS. On the one hand, lncRNAs regulate cancer progression as AS products of precursor messenger RNA (mRNA), but on the other hand, precursor lncRNA generates cancer-related abnormal splicing variants through AS. In addition, lncRNAs directly or indirectly regulate the AS events of downstream target genes, thus affecting the occurrence and development of cancer. Here, we reviewed how lncRNAs regulate AS and influence oncogenesis in different ways.Subject terms: Non-coding RNAs, Cancer genetics     

长链非编码RNA AFAP1-AS1在癌症中作用及其机制的研究进展

癌症一直是全球非感染性疾病死亡的主要原因之一,癌症的有效筛查和早期诊断、早期治疗一直以来是临床的一大难点,鉴定新的生物标志物或分子靶标以改善癌症患者的诊断和治疗刻不容缓.近年来研究发现,长链非编码RNA(long non-coding RNA,lncRNA)是一系列生物行为和包括肿瘤在内的疾病发生、发展的主要调节因子,...     

Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate gastric cancer progression

Background

Long noncoding RNAs (lncRNAs) have recently emerged as important regulators in governing fundamental biological processes, and many of which are likely to have functional roles in tumorigenesis. Maternally expressed gene 3 (MEG3) gene encodes a lncRNA whose expression is lost in an expanding list of primary human tumors and tumor cell lines, however its biological role and regulatory mechanism in gastric cancer (GC) development and progression are poorly defined.

Methods

Quantitative RT-PCR analysis was used to determine whether aberrant MEG3 expression was associated with GC patients pTNM stage and pM state. Furthermore, the effect of ectopic expression of MEG3 on cell proliferation, migration, invasion and cell apoptosis was assessed by using CCK-8, wound healing, transwell invasion assays and flow cytometric analysis, respectively, in GC cell lines HGC-27 and MGC-803. Moreover, the competing endogenous RNA (ceRNA) activity of MEG3 on miR-181a was investigated via luciferase reporter assay and immunoblot analysis.

Results

MEG3 is decreased in GC patients and cell lines, and its expression was associated with metastatic GC. Furthermore, ectopic expression of MEG3 in HGC-27 and MGC-803 cells inhibited cell proliferation, migration, invasion, and promoted cell apoptosis, which might be due to MEG3 sequestering oncogenic miR-181 s in GC cells. Furthermore, MEG3 could up-regulated Bcl-2 via its competing endogenous RNA (ceRNA) activity on miR-181a.

Conclusions

These findings suggest that lncRNA MEG3, a ceRNA of miR-181 s, could regulate gastric carcinogenesis and may serve as a potential target for antineoplastic therapies.