m6A甲基化在肿瘤发生发展中作用的研究进展

近年来,表观遗传修饰在恶性肿瘤发生发展中的调控作用受到广泛关注。早期的表观遗传修饰研究主要集中于DNA 和蛋白质水平,随着RNA深度测序技术和生物信息学方法的发展, 以N6-甲基腺嘌呤（N6-methyladenosine, m6A）为主的RNA表 观遗传修饰逐渐成为生物科学领域的研究热点。m6A是存在于所有高等真核生物中最普遍的mRNA表观修饰,具有动态可逆的 特点,涉及许多复杂细胞过程的精细调控, 如RNA的加工、运输、定位、翻译及降解等。最新研究表明, m6A可通过“写入”、“擦 除”和“阅读”相关因子的异常表达,可逆地动态调节RNA运输、定位、翻译及降解等方面,通过多种机制在肿瘤的发生发展过程 中发挥促进或抑制作用。本文就近年来m6A的生物学特性、RNA修饰的调控机制及其在肿瘤发生发展中的作用研究进展作一综述。     

RNA甲基化修饰在肿瘤中的作用研究进展

目前已有150多种RNA甲基化修饰被确认为真核生物转录后调控标记.随着研究的不断深人,RNA甲基化修饰在癌症发生发展过程中的作用引起了越来越多的关注,但RNA甲基化修饰在肿瘤中的发生发展机制仍有待阐明.全文对RNA甲基化修饰类型、RNA甲基化修饰在肿瘤中的作用进行了总结,并对RNA甲基化修饰在肿瘤研究中所面临的挑战和未...     

m6A RNA甲基化在非小细胞肺癌中的研究进展

m6A修饰是真核生物mRNA中最丰富的修饰之一,该过程受m6A甲基转移酶和去甲基化酶的共同调控.m6A修饰后的RNA能够被m6A识别蛋白特异性识别并结合,进而介导RNA的剪接、成熟、出核、降解和翻译等.目前国内外对于m6A修饰及其相关蛋白如何参与非小细胞肺癌发生发展的研究,主要集中于细胞恶性增殖、迁移、侵袭、转移和耐药...     

N6-甲基腺苷甲基化修饰与结直肠癌关系的研究进展

N6-甲基腺苷(m6A)甲基化是真核生物细胞RNA中常见修饰方式之一,其作用包括对RNA进行剪接、转运、定位、翻译和调控RNA的稳定性.m6A甲基化调节因子异常与众多疾病相关,包括多种肿瘤、心血管疾病以及代谢性疾病.越来越多的研究表明,在结直肠癌组织中发现的RNA中m6A修饰的异常调节对于肿瘤的发生、发展及转移至关重要...     

RNA甲基化修饰在胶质母细胞瘤发生发展中的研究进展

胶质母细胞瘤（glioblastoma,GBM）是一种高度恶性的原发性中枢神经系统肿瘤,患者预后差。RNA甲基化修饰作为一种广泛研究的表观遗传机制,已被证明在肿瘤的发生和发展中发挥重要作用。该文旨在探讨各种RNA甲基化修饰方式在GBM发生发展中的研究进展,为探索更有效的治疗策略提供新方向。     

N6-甲基腺嘌呤修饰在恶性肿瘤发生发展及治疗中的研究进展

近年来RNA修饰引起了全世界生物学家的广泛关注。到目前为止已发现170余个RNA修饰,其中N6-甲基腺嘌呤(m6A)是mRNA最主要的修饰方式之一。它调节RNA的剪接、转位、翻译和稳定性,在细胞的生长、分化和代谢中起着至关重要的作用。作为一种动态、可逆的修饰,m6A的表达水平受RNA甲基转移酶、去甲基酶以及m6A结合蛋白的共同调节。越来越多的研究表明m6A基因修饰与人类癌症的发生发展关系密切。本文就m6A异常修饰在多种恶性肿瘤发生发展及治疗中的研究进展进行综述,旨在为癌症治疗提供新的思路。     

RNA的N6-甲基腺嘌呤甲基化在肿瘤发生中作用的研究进展

RNA的N⁶-甲基腺嘌呤（m⁶A）甲基化是RNA修饰的最主要形式,参与m⁶A甲基化与去甲基化过程的酶分为3类：甲基转移酶,去甲基酶和m⁶A结合蛋白。这3类调控m⁶A的蛋白在RNA的加工代谢以及正常生理功能中发挥重要的调节作用,并且通过调节RNA的转录、剪接、加工、翻译和衰变等过程参与多种恶性肿瘤的发生和转移。近年来随着m⁶A检测技术的发展,m⁶A甲基化在恶性肿瘤病理进程中的作用研究逐渐成为热点。本文就有关m⁶A甲基化修饰影响肿瘤病程的表观遗传学机制进行综述,旨在为以m⁶A甲基化为靶点的肿瘤治疗策略提供新思路。     

RNA m5C甲基化修饰在肿瘤中的研究进展

5-甲基胞嘧啶(5-methylcytosine,m5C)是RNA中重要的甲基化修饰之一,也是近年来的研究热点.随着甲基化测序技术的发展,在编码RNA及非编码RNA中均证实存在大量的m5C甲基化修饰.RNA m5C甲基化修饰受m5C甲基转移酶、去甲基化酶及m5C甲基化结合蛋白的调控.m5C甲基化修饰调节RNA的稳定性、...     

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。     

N6-甲基腺苷修饰及其在胃癌化疗耐药作用中的研究进展

胃癌是我国最常见的消化系统恶性肿瘤,其化疗耐药问题日趋严重,导致治疗有效率下降。N6-甲基腺苷（m6A）修饰作为真核生物中最丰富的RNA内部修饰,影响RNA的加工、调节mRNA翻译效率和稳定性,在胃癌中调控肿瘤基因和蛋白的表达水平,导致肿瘤细胞对化疗产生抵抗。m6A修饰在胃癌化疗耐药中的双重作用可为平衡机体获得耐药过程提供思路。全文对m6A修饰及其在胃癌化疗耐药中的功能和作用机制的研究进展等进行综述,以期为临床防治m6A修饰失衡引起的胃癌化疗耐药提供理论参考及依据。     

Constructing and validating of m7G-related genes prognostic signature for hepatocellular carcinoma and immune infiltration: potential biomarkers for predicting the overall survival

BackgroundTo investigate the prognostic significance of N7-methylguanosine (m7G) regulators and immune infiltration in liver hepatocellular carcinoma (LIHC).MethodsThe research measured predictive m7G genes in LIHC samples from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. Data on the stemness index based on mRNA expression (mRNAsi), gene mutations, and corresponding clinical characteristics were obtained from TCGA and ICGC. Lasso regression was used to construct the prediction model to assess the m7G prognostic signals in LIHC. Based on these genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify key biological functions and pathways. The correlation between m7G RNA methylation regulators and the prognosis and immune infiltration of LIHC was evaluated.ResultsThere were 21 m7G-related differentially expressed genes (DEGs) in LIHC and healthy tissues, and LIHC patients could be divided into two categories by consensus clustering of these DEGs. A five-gene predictive approach was employed using least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Patients in the low-risk group showed a significantly higher survival rate compared with those in the high-risk group (P=0.001). Validations using the ICGC database. Also, univariate and multivariate Cox regression analyses suggested that the risk score produced by the predictive model is an independent predictor for LIHC [hazard ratio (HR): 1.848, 95% confidence interval (CI): 1.286–2.656; HR: 2.597, 95% CI: 1.358–4.965]. The ROC curves of the ICGC cohort revealed that the five-gene prediction model performed well [area under the curve (AUC) =0.642 at 1 year, AUC =0.686 at 2 years, and AUC =0.667 at 3 years]. Immuno-oncology scoring revealed that in the high-risk group, among 16 immune cells, the expressions of neutrophils and natural killer (NK) cells were low and that of regulatory T-cells (Tregs) was high.ConclusionsLIHC occurrence and progression are linked to m7G-related genes. Corresponding prognostic models help forecast the prognosis of LIHC patients. m7G-related genes and associated immune cell infiltration in the TME may serve as potential therapeutic targets in LIHC, which requires further trials. In addition, the m7G-related gene signature offers a viable alternative to predict LIHC, and these m7G-related genes show a prospective research area for LIHC targeted treatment in the future.     

m6A甲基化修饰酶ZC3H13的功能及其在肿瘤中的研究进展

N6甲基腺苷化(N6-methyladenosine,m6A)mRNA修饰在细胞分化和肿瘤发生中具有重要作用,也是近几年表观转录组学的研究热点。ZC3H13(zinc finger CCCH domain-containing protein 13)是m6A甲基转移酶复合体中的新型调控蛋白,其介导的m6A修饰在肿瘤的发生发展中起着重要作用,因此可能成为新的肿瘤表观遗传调节剂。本文将阐述一种新的mRNA m6A甲基化修饰酶ZC3H13的结构、功能及其在肿瘤中的研究进展,旨在为基础医学及临床治疗中m6A修饰的研究提供新的研究思路和治疗靶点。     

m6A修饰在肿瘤细胞自噬中的作用

自噬是一种细胞自我降解过程,在维持细胞和生物体代谢功能中起着至关重要的作用。自噬功能失调与包括肿瘤在内的多种疾病有关。m⁶A修饰作为真核生物体内主要的RNA内部修饰,通过影响自噬相关基因（autophagy associated gene,ATG）的表达或干扰自噬相关信号通路在调节肿瘤细胞自噬过程中发挥重要作用,异常的m⁶A修饰会导致自噬失调并影响肿瘤的进展。然而,其在肿瘤自噬调控中的具体作用仍待探索。因此,本文综述了m⁶A修饰在肿瘤细胞自噬中的作用,并探讨了其与肿瘤进展及其耐药的关系,旨在为开发新的治疗策略提供理论基础。     

m6A与mRNA代谢及其与恶性肿瘤关系的研究进展

N6-甲基腺嘌呤（N6-methyladenosine,m6A）为高等真核生物信使RNA（messenger RNA,mRNA）中最普遍的内部修饰,几乎影响mRNA代谢的每个步骤,包括mRNA的加工、核输出、翻译以及降解等。该修饰过程由m6A修饰酶:甲基转移酶和去甲基化酶以动态可逆的方式进行调控。此外生物体中还存在能与m6A特异性识别结合并介导其行使一定生物学功能的m6A结合蛋白。最近,越来越多的研究发现m6A与恶性肿瘤有关,有助于肿瘤干细胞的自我更新,促进恶性肿瘤细胞增殖等。m6A与恶性转化的表型及机制密切相关,表现出m6A靶向治疗人类恶性肿瘤的可能性。换言之,m6A可能成为恶性肿瘤治疗的新靶标。本文旨在对m6A如何调控mRNA代谢及其与恶性肿瘤的关系进行综述。     

RNA修饰在肿瘤线粒体中的作用：机遇与挑战

碱基或核糖上发生化学基团修饰在RNA分子中普遍存在,这些RNA修饰行为可以通过影响基因表达从而调控肿瘤进展。深入研究RNA修饰在肿瘤进展中的作用,对于肿瘤机制的理解和干预策略的开发具有重要科学价值。线粒体在维持肿瘤细胞的异常代谢状态中扮演着至关重要的角色,近期研究提示RNA修饰与肿瘤线粒体之间存在着紧密联系,为干预肿瘤线粒体功能提供了重要机遇。本文聚焦于RNA修饰在肿瘤线粒体中的作用及相关机制,阐述线粒体自身及线粒体外RNA修饰对线粒体功能的影响,并探讨基于RNA修饰对肿瘤线粒体的干预策略,从而为代谢调控机制以及创新治疗策略提供更多的启示。

     

Estimating the prognosis of esophageal squamous cell carcinoma based on The Cancer Genome Atlas (TCGA) of m6A methylation-associated genes

BackgroundN6-methyladenosine (m6A) mRNA modification is the most prevalent in certain tumors. However, its expression profile and prognostic value in human esophageal squamous cell carcinoma (ESCC) remains unknown.MethodsHerein, we performed an extensive investigation of the m6A-associated gene expression profile and determined its significance in the prognosis of ESCC. We received the RNA expression profiles of 81 ESCC tissues and one normal esophageal tissue from The Cancer Genome Atlas (TCGA) database. Kaplan-Meier (KM) survival analysis was used to assess the predictability of m6A methylation-associated gene expression in ESCC prognosis. In addition, univariate and multivariate Cox regression, as well as least absolute shrinkage and selection operator (LASSO) regression models were employed for the establishment of prognostic signatures. Lastly, KM survival analysis, proportional hazard models, and receiver operating characteristic (ROC) curves were used to verify the prognostic value. Moreover, we also investigated the associations among the m6A prognostic signature, immune cell infiltration, and programmed cell death-ligand 1 (PD-L1) expression.ResultsWe demonstrated that YTHDF3 [hazard ratio (HR): 0.910; 95% confidence interval (CI): 0.832–0.995; P=0.038], RBM15 (HR: 0.721; 95% CI: 0.549–0.948; P=0.019), KIAA1429 (HR: 0.801; 95% CI: 0.664–0.967; P=0.021), and ALKBH5 (HR: 0.948; 95% CI: 0.895–1.003; P=0.0.064) overexpression predicted better overall survival (OS) of ESCC patients. Furthermore, based on prognostic factors, the high-risk (H-R) cohort was found to have worse survival than the low-risk (L-R) cohort (P<0.001).ConclusionsWe revealed three m6A methylation-associated genes that were closely correlated with enhanced survival in ESCC patients. In addition, we generated an independent prognostic signature based on the expression of YTHDF3, RBM15, KIAA1429, and ALKBH5 genes. The results revealed significantly higher proportions of CD8⁺ T cells and higher expression of PD-L1 in the H-R group.     

Long non-coding RNA small nucleolar RNA host gene 7 facilitates the proliferation,migration, and invasion of esophageal cancer cells by regulating microRNA-625

BackgroundEsophageal cancer (EC) is a highly aggressive malignant tumor, of which esophageal squamous cell carcinoma (ESCC) constitutes the main subtype. Long non-coding RNA (lncRNA) small nucleolar RNA host gene 7 (SNHG7) has been extensively studied in many tumors and has been confirmed to be an oncogene; however, it has yet to be investigated in an ESCC study. Therefore, this study intended to uncover the role of SNHG7 in ESCC.MethodsQuantitative real-time polymerase chain reaction was applied to measure the expression levels of SNHG7 and miR-625 in ESCC tumor tissues and cell lines. Cell Counting Kit-8 assay, 5-Ethynyl-2''-deoxyuridine assay, scratch assay, and Transwell assay were conducted to assess the proliferation, migration, and invasion ESCC cell. We verified the interaction between SNHG7 and miR-625 by performing the dual luciferase reporter gene experiment.ResultsCompared to that in adjacent normal tissues and HET1A cell lines, the expression level of SNHG7 in ESCC tumor tissues and ESCC cell lines was up-regulated, while the expression level of miR-625 was down-regulated. ESCC cell proliferation, migration, and invasion were significantly promoted by SNHG7 overexpression but inhibited by silencing of SNHG7. Further, luciferase reporter gene experiments confirmed that SNHG7 interacted with miR-625, and rescue experiments showed that SNHG7 promoted the malignant phenotype by inhibiting miR-625.ConclusionsSNHG7 is up-regulated in ESCC tumor tissues and cell lines, while miR-625 is expressed at a low level. SNHG7 is able to facilitate the proliferation, migration, and invasion of ESCC cells by targeting miR-625.