LncRNA MEG3在骨肉瘤组织中的表达及对MG-63细胞增殖、凋亡与侵袭的影响

目的探讨长链非编码RNA母系印记基因3(lncRNA MEG3)在骨肉瘤组织中的表达及对人骨肉瘤细胞MG-63增殖、凋亡与侵袭的影响。方法实时荧光定量PCR(qPCR)方法检测5例骨肉瘤组织及癌旁对应正常组织中lncRNA MEG3的表达水平。构建pcDNA3.1-MEG3重组质粒,MEG3过表达后,MTT方法检测MG63细胞增殖能力的变化;流式细胞术检测MG63细胞的凋亡率;Transwell实验检测MG63细胞侵袭能力的变化;Western blot方法检测MG63细胞增殖细胞核抗原(PCNA)与Racl蛋白的表达变化。结果 lncRNA MEG3在骨肉瘤组织中的表达显著低于癌旁正常组织(P0.01)。lncRNA MEG3过表达后,MG63细胞的增殖与侵袭能力显著降低,凋亡率显著上升,PCNA与Racl蛋白的表达显著降低(P0.01)。结论 lncRNA MEG3在骨肉瘤组织中低表达,过表达lncRNA MEG3能够抑制人骨肉瘤细胞MG-63的增殖与侵袭,并促进凋亡。     

长链非编码RNA在癫痫中的作用及研究进展

长链非编码RNA(lncRNA)是人类基因组中不能编码蛋白质,分子长度大于200nt的RNA,lncRNA是非编码RNA(nc RNA)中的一种,占nc RNA的80%,仅以分子的形式发挥作用,在过去的研究中lncRNA被认为是不重要的"噪音",但是近年来对lncRNA的功能研究显示其同样具有重要作用,lncRNA能在转录、转录后和表观遗传学上进行调控,参与个体发育中重要的生理和病理生命发育过程,lncRNA异常的表达对人类多种疾病的发生有密切的关系,本综述就癫痫发生发展密切相关的lncRNA进行阐述。     

长链非编码RNA与运动障碍疾病

长链非编码RNA(Long non-coding RNA,lncRNA)是一类长度超过200个核苷酸的不具有蛋白质编码功能的RNA,研究发现它们参与调控神经元的发育与再生,在中枢退行性疾病中差异表达。LncRNA通过影响附近蛋白质基因的编码调控其生物学功能,而运动障碍疾病与中枢基底神经节神经元内蛋白质基因的异样表达有关,本文综述近期有关lncRNA及其相关蛋白质基因在运动障碍疾病发病机制中的研究进展。     

长链非编码RNA作为自身免疫病生物标志物的研究进展

长链非编码RNA(long non-coding RNA,lncRNA)指不编码蛋白质的基因转录产物,参与多种生物学过程,其异常表达与许多疾病有关.lncRNA在免疫调节中发挥重要作用,参与固有免疫与适应性免疫过程,与自身免疫性疾病有关.近年来研究发现,lncRNA可在mRNA转录、蛋白质翻译和修饰等过程中发挥调控作用...     

长链非编码RNA在肿瘤研究中的进展

长链非编码RNA(long non-coding RNA,lncRNA)是细胞中一类转录本长度超过200个核苷酸的非编码RNA分子,本身并不编码蛋白或很少有编码蛋白质功能,在哺乳动物基因组普遍被转录。起初认为它是转录过程中的副产物,不具有生物学功能。随着研究的深入,新的lncRNA不断被发现,越来越多的证据显示lncRNA具有复杂的生物学功能,并与人类疾病的发生关系密切。     

柚皮苷调控lncRNA MEG3/Wnt/β-catenin信号通路促进炎症来源牙周膜干细胞的成骨分化北大核心CSCD

目的:研究柚皮苷对炎症来源牙周膜干细胞成骨分化的影响及其作用机制。方法:分离培养牙周炎来源的牙周膜干细胞(PPDLSCs)和正常牙周组织来源的牙周膜干细胞(HPDLSCs),PPDLSCs转染小干扰RNA(siRNA)阴性对照组和lncRNA MEG3 siRNA,采用1μmol/L柚皮苷干预PPDLSCs并进行成骨分化诱导,RT-qPCR和Western blot实验检测lncRNA MEG3和成骨分化相关基因OCN、Runx2、ALP的表达,Western blot检测Wnt/β-catenin信号通路相关蛋白GSK3β、p-GSK3β、β-catenin的表达。结果:柚皮苷干预促进PPDLSCs中OCN、Runx2和ALP mRNA和蛋白表达,促进PPDLSCs的成骨分化;与HPDLSCs相比,PPDLSCs中lncRNA MEG3相对表达量降低,柚皮苷干预上调PPDLSCs中lncRNA MEG3的表达;抑制lncRNA MEG3能够抑制PPDLSCs细胞增殖,并减弱柚皮苷对PPDLSCs成骨分化的促进作用;柚皮苷干预抑制PPDLSCs中p-GSK3β、β-catenin蛋白表达,抑制Wnt/β-catenin通路活性,而抑制lncRNA MEG3能够减弱柚皮苷对Wnt/β-catenin通路活性的抑制作用。结论:柚皮苷能够促进PPDLSCs的成骨分化,其作用机制可能与上调lncRNA MEG3表达,抑制Wnt/β-catenin通路活性有关。     

长链非编码RNA在表观遗传学中的研究进展

表观遗传学是基于遗传学基础之上发展起来的生物学分支,研究发现人类很多疾病与表观遗传调控相关,其主要机制包括:染色质重塑、组蛋白修饰,基因组印记及非编码RNA(ncRNA)调控.而长链非编码RNA(lncRNA)是非编码RNA中的一类,不仅可以通过与靶基因直接结合调控靶基因的转录,还能募集调控因子,参与基因的沉默,在表观遗传调控中起着重要作用.     

非编码RNA与高血压关系研究进展

非编码RNA(ncRNA)是人类基因组的重要组成部分,主要包括微小RNA(miRNA)和长链非编码RNA(lncRNA)两种类型。miRNA在高血压发病机制中起重要作用,靶向miRNA或可成为治疗高血压新策略;lncRNA在高血压中也被发现呈现异常表达。miRNA和lncRNA还可能成为高血压及相关疾病诊断的生物标志物。     

TP73-AS1在肿瘤中的表达及调控作用

<正>随着高通量测序技术的发展,成千上万种长链非编码RNA(long non-coding RNA,lncRNA)进入人们的视野。lncRNA是一类长度超过200个核苷酸并缺少开放阅读框的不具备蛋白质编码功能的RNA~([1-2])。研究发现lncRNA参与诸多生物学进程的关键步骤,包括染色质重塑、基因转录、转录后调节和蛋白质翻译等~([3-5])。LncRNA机制的不断被阐明,也为肿瘤的研究提供了新的可能。LncRNA在多种肿瘤的增殖、迁移侵袭和抗凋亡     

牛磺酸上调基因1对肿瘤发生发展的调控作用

<正>基因的失调控(异常表达)是肿瘤发生发展的重要原因(诱因)业已被学术界所公认,而在这一过程中非编码RNA(non-coding RNA,ncRNA)起到了极为重要的调控作用~([1-2])。小RNA(small RNA;包括微小RNA,microRNA,miRNA,miR)和长链非编码RNA(long non-coding RNA,lncRNA)均属于ncRNA~([3-4])。     

MEG3 LncRNA from Exosomes Released from Cancer-Associated Fibroblasts Enhances Cisplatin Chemoresistance in SCLC via a MiR-15a-5p/CCNE1 Axis

PurposeLong non-coding RNAs (lncRNAs) may act as oncogenes in small-cell lung cancer (SCLC). Exosomes containing lncRNAs released from cancer-associated fibroblasts (CAF) accelerate tumorigenesis and confer chemoresistance. This study aimed to explore the action mechanism of the CAF-derived lncRNA maternally expressed gene 3 (MEG3) on cisplatin (DDP) chemoresistance and cell processes in SCLC.Materials and MethodsQuantitative real-time PCR was conducted to determine the expression levels of MEG3, miR-15a-5p, and CCNE1. Cell viability and metastasis were measured by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-h-tetrazolium bromide and invasion assays, respectively. A xenograft tumor model was developed to confirm the effect of MEG3 overexpression on SCLC progression in vivo. Relationships between miR-15a-5p and MEG3/CCNE1 were predicted using StarBase software and validated by dual luciferase reporter assay. Western blotting was used to determine protein levels. A co-culture model was established to explore the effects of exosomes on MEG3 expression in SCLC cell lines.ResultsMEG3 was overexpressed in SCLC tissues and cells. MEG3 silencing significantly repressed cell viability and metastasis in SCLC. High expression of MEG3 was observed in CAF-derived conditioned medium (CM) and exosomes, and promoted chemoresistance and cancer progression. Additionally, MEG3 was found to serve as a sponge of miR-15a-5p to mediate CCNE1 expression. Overexpression of miR-15a-5p and knockout of CCNE1 reversed the effects of MEG3 overexpression on cell viability and metastasis.ConclusionMEG3 lncRNA released from CAF-derived exosomes promotes DDP chemoresistance via regulation of a miR-15a-5p/CCNE1 axis. These findings may provide insight into SCLC therapy.     

长链非编码RNAs的生物功能及其与器官发育和恶性肿瘤的关系

<正>在组成人类的约30亿个碱基对中,蛋白编码序列只占1.5%,而其余不编码蛋白质的序列曾一度被认为是基因组进化过程中的"垃圾序列"。2013年发布的ENCODE研究数据表明,所谓的"垃圾序列"绝大多数被转录成分子长度超过200个核苷酸的长链非编码RNAs(long noncoding RNAs,lncRNAs)。     

Long noncoding RNA-mediated anti-apoptotic activity in murine erythroid terminal differentiation

Long noncoding RNAs (lncRNAs) are differentially expressed under both normal and pathological conditions, implying that they may play important biological functions. Here we examined the expression of lncRNAs during erythropoiesis and identified an erythroid-specific lncRNA with anti-apoptotic activity. Inhibition of this lncRNA blocks erythroid differentiation and promotes apoptosis. Conversely, ectopic expression of this lncRNA can inhibit apoptosis in mouse erythroid cells. This lncRNA represses expression of Pycard, a proapoptotic gene, explaining in part the inhibition of programmed cell death. These findings reveal a novel layer of regulation of cell differentiation and apoptosis by a lncRNA.     

Differential expression of long non-coding RNAs during genotoxic stress-induced apoptosis in HeLa and MCF-7 cells

Long non-coding RNAs (lncRNAs) are emerging as new players in cancer as they are implicated in diverse biological processes and aberrantly expressed in a variety of human cancers. No data are available on their function under genotoxic stress-induced apoptosis. In this work, we assessed the behavior of some candidate lncRNAs (HOTAIR, MALAT1, TUG1, lincRNA-p21, GAS5, MEG3, PANDA, UCA1, ANRIL, and CCND1) during DNA damage-induced cell death in HeLa and caspase-3-deficient MCF-7 cells using bleomycin (BLM) and γ-radiation to induce DNA damage. Cells were incubated in the presence of BLM for 24 h or irradiated. Apoptosis was analyzed by measurement of oligonucleosomal fragmentation of nuclear DNA. Our results reveal that basal RNA expression levels as well as the changes in the lncRNA expression rates during genotoxic stress-induced apoptosis were cell-type and/or DNA-damaging agent-specific. Generally, we found that some of the RNA molecules (HOTAIR and MALAT1) are down-regulated while many of them (lincRNA-p21, GAS5, MEG3, ANRIL, and ncRNA-CCND1) are up-regulated and some others (TUG1, UCA1, and PANDA) not affected. The decline in the expression of HOTAIR (approx. twofold, p < 0.01) and MALAT1 (approx 1.6-fold, p < 0.01) was clearly evident in BLM-treated HeLa and MCF cells (only HOTAIR, fivefold, p < 0.01). For lincRNA-p21, ncRNA-CCND1, and MEG3, a similar up-regulation pattern was obvious in both cell lines where the increase was generally more pronounced in BLM-treated cells. Interestingly, the induction of ANRIL and GAS5 was mainly restricted to irradiated cells. In conclusion, our findings reveal a differential regulation of individual lncRNAs during genotoxic stress-induced apoptosis.     

lncRNA MEG3 restrained the M1 polarization of microglia in acute spinal cord injury through the HuR/A20/NF‐κB axis

The M1 polarization of microglia and neuroinflammation restrict the treatment of acute spinal cord injury (ASCI), and long non‐coding ribonucleic acid (lncRNA) maternally expressed gene 3 (MEG3) expression is lessened in ASCI. However, the function and mechanism of lncRNA MEG3 in the M1 polarization of microglia and neuroinflammation in ASCI are unclear. The expressions of lncRNA MEG3 in ASCI mouse spinal cord tissues and lipopolysaccharide (LPS)‐treated primary microglia and BV2 cells were quantified through a quantitative real‐time polymerase chain reaction. In‐vitro assays were conducted to explore the function of lncRNA MEG3 in the M1 polarization of microglia and neuroinflammation in ASCI. RNA degradation, RNA immunoprecipitation, RNA pull‐down, cycloheximide‐chase, and ubiquitination analyses were carried out to probe into the mechanism of lncRNA MEG3 in the M1 polarization of microglia and neuroinflammation in ASCI. The lncRNA MEG3 expression was lessened in the ASCI mouse spinal cord tissues and LPS‐treated primary microglia and BV2 cells, and the overexpression of lncRNA MEG3 restrained the M1 polarization of microglia and the neuroinflammation by regulating the NF‐κB signaling pathway. For the investigation of the potential mechanism of such, the overexpression of lncRNA MEG3 restrained the M1 polarization of microglia through the HuR/A20/NF‐κB axis and boosted the motor function recovery and neuroinflammation relief in the mice with SCI. The overexpression of lncRNA MEG3 restrained the M1 polarization of microglia through the HuR/A20/NF‐κB axis.     

Long non-coding RNAs in retinoblastoma

Retinoblastoma represents 3% of all childhood cancers and is the most common intraocular malignant tumor with a highly aggressive and metastatic phenotype. While recent genetic and epigenetic studies have reported new insights into the mechanism of retinoblastoma development, the involvement of regulatory non-coding RNAs remains unclear. Long non-coding RNAs (lncRNAs) are a group of endogenous non-protein-coding RNAs with the capacity to regulate gene expression at multiple levels. Recent evidence has shown that lncRNAs can regulate many cellular processes, such as cell proliferation, differentiation, migration, and invasion. Several lncRNAs, including BANCR, AFAP1-AS1, NEAT1, XIST, ANRIL, PlncRNA-1, HOTAIR, PANDAR, DANCR, and THOR, promote the progression and metastasis of retinoblastoma. However, some lncRNAs, such as MEG3, MT1JP, and H19, play a tumor suppressive role. Our review summarizes the functional role of lncRNAs in retinoblastoma and their potential clinical applications for diagnosis, prognosis, and treatment.