胃癌转移相关微小RNA的研究进展

胃癌是我国最常见的恶性肿瘤之一,复发和转移仍就是胃癌治疗的一大难题.微小RNA(miRNA)是一类内源性非编码小RNA,在转录后水平对基因表达进行负调控.可以作为一类新型的癌基因或抑癌基因参与肿瘤的凋亡,生长,侵袭.研究miRNA对胃癌转移发生发展的作用有助于我们寻找治疗胃癌的新方法.本文就miRNA和胃癌转移关系的研究进展做一综述.     

miRNA与siRNA胃癌相关研究的现状及进展

RNA干扰是表观遗传学的研究热点,它参与基因复制后表达调控,并与肿瘤发生密切相关。近年对RNA干扰研究较多的是微小RNA和小干扰RNA。文章概述了微小RNA和小干扰RNA的基本理论,并综述它们在胃癌研究中的现状及进展。认为RNA干扰分析和应用是研究胃癌相关基因功能及作用机制的有效方法,并将对胃癌的诊治产生巨大影响。     

长链非编码RNA在胃癌中的研究进展

长链非编码RNA(1ong non-coding RNA,lnc RNA)是一组长度超过200 bp、缺少特异开放阅读框、不具备完整蛋白编码功能的RNA,其在表观遗传学调控以及转录和转录后调控等方面发挥重要作用。目前,在乳腺癌和肝癌中对Lnc RNA的研究颇多,而对胃癌中Lnc RNA的报道却刚刚兴起。近几年越来越多的研究发现,在胃癌中有很多特异表达的Lnc RNA与胃癌的发生、发展、侵袭、转移密切相关。本文结合国内外最新研究就lnc RNA在胃癌中的研究进展作一简要综述,主要介绍了Lnc RNA在肿瘤研究中的最新发现,尤其是其与胃癌发生发展的密切联系,旨在为胃癌的诊断和治疗提供新思路。     

胃癌相关miRNA表达的表观遗传学调控机制

胃癌是人类最常见的肿瘤之一,其发病机制尚不完全清楚.微小RNA(microRNA,miRNA)是一组最近发现的长度为22个核苷酸左右的非编码RNA,具有负性调控基因表达的功能.本文对miRNA在胃癌发生中的作用及其表达调控机制进行综述.不断有文献显示,miRNA在多种肿瘤(包括胃癌)的发生过程中发挥着重要作用.作者和其他研究人员发现,miRNA的表达异常(如:miR-421和miR-21的上调或/和miR-31和miR-218的下调等)与胃癌的发生相关,提示miRNA是胃癌发生的重要因素.目前,miRNA表达的分子机制尚未完全明了.最近研究较清楚地显示,miRNA的表达受到DNA甲基化和组蛋白修饰等机制的调控.这说明,胃癌相关miRNA的表达水平受到表观遗传机制的调控。     

微小RNA在恶性肿瘤靶向治疗中的研究进展

恶性肿瘤一直是当今世界最难攻克的顽疾之一,肿瘤靶向治疗以其高效低毒等特点为病人带来了新的希望,目前的靶向药物主要是单克隆抗体和小分子酪氨酸激酶抑制剂。微小RNA(micro RNA,mi RNA)是一类小的、进化保守的非编码RNA,负性调节编码基因以及非编码转录因子的表达,是各种细胞主要调控者,在肿瘤的发生、进展以及转移中发挥了重要的作用。研究显示,多种肿瘤均存在大量发挥癌基因或抑癌基因作用的mi RNA的表达失调,而这些表达异常的mi RNA已成为人们研制肿瘤靶向治疗的又一新工具。因此本研究就近年来mi RNA在肿瘤靶向治疗中的相关研究做一简要综述,以期为肿瘤的靶向治疗提供新的视角。     

胃癌淋巴结微转移的临床研究进展

胃癌是我国目前最常见的恶性肿瘤之一,微转移是恶性肿瘤在发展过程中所形成的尚处于临床不可探测阶段的微小转移灶,播散并存活于淋巴系统、血液循环、骨髓、肝、肺等组织器官中,是恶性肿瘤复发和转移的根源。目前对胃癌淋巴结微转移的深入研究主要集中在通过寻找不同的检测方法、途径和特异性肿瘤标志物,对常规检查淋巴结为阴性的胃癌,微转移检测可能对准确地确定临床分期、指导治疗、判断预后有积极临床意义。现就胃癌微转移检测研究的现状和存在的问题予以综述。     

微小RNA通过调控肿瘤血管形成影响肿瘤转移

肿瘤转移的过程是一个连续的、相互关联的级联事件,整个过程受多因素、多基因调控。血管形成是肿瘤转移的前提和基础,抑制肿瘤血管生成是控制肿瘤转移的一个可行策略。微小RNA(micro RNAs,mi RNAs)是一类非编码的小分子RNA,可在转录后水平调控肿瘤血管生成,在肿瘤的转移过程中起着至关重要的作用。本文主要就mi RNAs调控肿瘤血管形成参与肿瘤转移过程中的最新研究进展进行了综述。     

幽门螺杆菌相关miRNA与胃癌关系的研究进展

微小核糖核酸(microRNA,miRNA)是一种由内源基因编码长度约为22个核苷酸的非编码RNA,其能抑制靶基因蛋白质表达,有多种生物学功能。越来越多的研究表明,miRNA在多种肿瘤中异常表达,参与肿瘤发生、发展过程。幽门螺杆菌(Helicobacter pylori,Hp)作为胃癌的主要致病因素,可通过调节miRNA的表达,在胃癌中起促进或抑制作用。现就Hp相关miRNA在胃癌中的作用作一概述。     

外泌体在白血病中的重要调控作用

目前,白血病复发是患者死亡的主要原因之一。肿瘤细胞和微环境的相互作用,以及隐匿在骨髓中的肿瘤干细胞,促进了白血病的复发和向淋巴组织的转移,因此白血病的治疗、转移和复发问题受到广泛关注。外泌体是由绝大多数细胞分泌的双层脂质膜囊泡,可以调控细胞间的交流和信息传递。在白血病细胞、基质细胞和内皮细胞之间的相互联系中都涉及到外泌体,白血病细胞来源的外泌体存在于白血病患者的血浆中,能把其携带的白血病相关抗原及微小RNA呈递给靶细胞,促进白血病肿瘤细胞的增殖,有助于肿瘤细胞实现免疫逃避,保护白血病细胞抵抗化疗药物导致的细胞毒性作用,促进血管生成及肿瘤细胞的迁移。因此,外泌体与白血病的转移、治疗及预后密切相关,可以用来检测和监测白血病的进展。本文综述了外泌体的来源、形成与分泌机制,以及外泌体在白血病发生前、发展中、预后和免疫治疗中所扮演的重要角色。     

蜜蜂非编码RNA研究进展

非编码RNA(Non-coding RNA,ncRNA)是指不编码蛋白质的功能性RNA的统称,主要包括微小RNA(MicroRNA,miRNA)、长链非编码RNA(Long non-coding RNA,lncRNA)和环状RNA(Circular RNA,circRNA)等,它们在各种生命活动中发挥着重要的调控作用.蜜蜂不仅是重要经济授粉昆虫,还是人类研究动物复杂社会行为的最佳模式生物.近年来,蜜蜂ncRNA亦是该领域研究热点,成果不断涌现,本文在介绍ncRNA的特征、分类及其主要作用机制的基础上,主要针对ncRNA在蜜蜂劳动分工、级型分化、繁殖性能和免疫防御等方面调控作用的最新研究进展进行综述,以期为深入探究ncRNA提供借鉴和参考.     

MicroRNA-650 targets ING4 to promote gastric cancer tumorigenicity

MicroRNAs (miRNAs) are non-coding RNAs that regulate the expression of target mRNAs. Altered expression of specific miRNAs in human gastric cancer progression has been reported; however, the role of miR-650 in gastric cancer is poorly understood. In this study, we show that miR-650 is involved in lymphatic and distant metastasis in human gastric cancer, and we find that ectopic expression of miR-650 promotes tumorigenesis and proliferation of gastric cancer cells. A luciferase reporter assay demonstrates that Inhibitor of Growth 4 (ING4) is a direct target of miR-650. Collectively, our study demonstrates that over-expression of miR-650 in gastric cancer may promote proliferation and growth of cancer cells, at least partially through directly targeting ING4. These findings help clarify the molecular mechanisms involved in gastric carcinogenesis and indicate that miR-650 modulation may be a bona fide miRNA-based treatment of gastric cancer.     

MicroRNA-34A inhibits the growth,invasion and metastasis of gastric cancer by targeting PDGFR and MET expression

Within the family of RTKs (receptor tyrosine kinases), PDGFR (platelet-derived growth factor receptor) has been implicated in carcinogenesis and tumour development. miRNAs (microRNAs), which can target the mRNAs (messenger RNAs) of cancer-associated genes, are abnormally expressed in various cancers. In this study, our aim was to identify the miRNAs that target PDGFR-α/β and to study the functions of these miRNAs. miR-34a was predicted to target PDGFR, and luciferase reporter assays showed that miR-34a could directly target PDGFR. Meanwhile, we found that miR-34a was down-regulated in gastric cancer tissues and was associated with metastasis. Our findings showed that miR-34a could inhibit gastric cancer cell migration, invasion and proliferation, but these tumourigenic properties were only partially restored when PDGFR-α/β was overexpressed. In subsequent experiments, we found that the overexpression of both PDGFR and MET could completely restore the gastric cancer tumourigenic properties. Moreover, the cancer-associated cell signalling pathway was studied, and we found that miR-34a could inhibit Akt [PKB (protein kinase B)] phosphorylation, which was restored by the overexpression of both PDGFR and MET. In conclusion, miR-34a may act as a potential tumour suppressor in gastric cancer and is associated with the mechanisms of gastric cancer metastasis; miR-34a can inhibit gastric cancer tumourigenesis by targeting PDGFR and MET through the PI3K (phosphoinositide 3-kinase)/Akt pathway.     

Regulation of cancer metastasis by microRNAs

MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs that have been found highly conserved among species. MiRNAs are able to negatively regulate gene expression through base pairing of 3’ UTRs of their target genes. Therefore, miRNAs have been shown to play an important role in regulating various cellular activities. Over the past decade, substantial evidences have been obtained to show that miRNAs are aberrantly expressed in human malignancies and could act as “OncomiRs” or “Tumor suppressor miRs”. In recent years, increasing number of studies have demonstrated the involvement of miRNAs in cancer metastasis. Many studies have shown that microRNAs could directly target genes playing a central role in epithelia-mesenchymal-transition (EMT), a cellular transformation process that allows cancer cells to acquire motility and invasiveness. EMT is considered an essential step driving the early phase of cancer metastasis. This review will summarize the recent findings and characterization of miRNAs that are involved in the regulation of EMT, migration, invasion and metastasis of cancer cells. Lastly, we will discuss potential use of miRNAs as diagnostic and prognostic biomarkers as well as therapeutic targets for cancer.     

Exosomal miRNAs as circulating biomarkers for prediction of development of haematogenous metastasis after surgery for stage II/III gastric cancer

Exosomes secreted by living cancer cells can regulate metastasis. Exosomal miRNAs can reflect pathological conditions of the original cancer cells. Therefore, we aim to identify exosomal miRNAs as circulating biomarkers for haematogenous metastasis of gastric cancer. Pre-treatment serum samples of eighty-nine patients with stage II/III gastric cancer were collected. Thirty-four of them developed haematogenous metastasis after surgery and the other fifty-five did not. Extraction of exosomes was validated by western blot, transmission electron microscopy and nanoparticle tracking analysis. MiRNA qPCR array was performed in three matched pairs of samples. Internal control was selected from PCR array and validated in the remaining samples. Expressions of exosomal miRNAs were evaluated in the remaining samples by RT-qPCR, as well as in gastric cancer tissue samples and cell culture medium. Expression levels of exosomal miRNAs were analysed with clinical characteristics. The results indicated thirteen up-regulated and six down-regulated miRNAs were found after normalization. MiR-379-5p and miR-410-3p were significantly up-regulated in metastatic patients (P < .01). Higher expression of exosomal miR-379-5p or miR-410-3p showed shorter progression-free survival of the patients (P < .05). It was also found that miR-379-5p and miR-410-3p were down-regulated in gastric cancer tissue samples, while they were significantly up-regulated in gastric cancer cell culture medium compared with cancer cells. In conclusion, exosomal miRNAs are promising circulating biomarkers for prediction of development of haematogenous metastasis after surgery for stage II/III gastric cancer.     

microRNAs in breast cancer: regulatory roles governing the hallmarks of cancer

A large number of etiological factors and the complexity of breast cancers present challenges for prevention and treatment. Recently, the emergence of microRNAs (miRNAs) as cancer biomarkers has added an extra dimension to the ‘molecular signatures’ of breast cancer. Bioinformatic analyses indicate that each miRNA can regulate hundreds of target genes and could serve functionally as ‘oncogenes’ or ‘tumour suppressor’ genes, and co‐ordinate multiple cellular processes relevant to cancer progression. A number of studies have shown that miRNAs play important roles in breast tumorigenesis, metastasis, proliferation and differentiation of breast cancer cells. This review provides a comprehensive overview of miRNAs with established functional relevance in breast cancer, their established target genes and resulting cellular phenotype. The role and application of circulating miRNAs in breast cancer is also discussed. Furthermore, we summarize the role of miRNAs in the hallmarks of breast cancer, as well as the possibility of using miRNAs as potential biomarkers for detection of breast cancer.     

MicroRNA-107, an oncogene microRNA that regulates tumour invasion and metastasis by targeting DICER1 in gastric cancer

MicroRNAs are small non-coding RNA molecules that control expression of target genes. Previous studies showed that microRNA-107 (miR-107) is overexpressed in gastric cancer tissues compared with the matched normal tissues. However, it remains largely unclear as to how miR-107 exerts its function and modulates the malignant phenotypes of gastric cancer, because our understanding of miR-107 signalling pathways is limited. In this study, we demonstrate that miR-107 is frequently up-regulated in gastric cancers and its overexpression is significantly associated with gastric cancer metastasis. Furthermore, silencing the expression of miR-107 could inhibit gastric cancer cell migration and invasion in vitro and in vivo. Subsequent investigation characterized DICER1 as a direct target of miR-107. Up-regulation of DICER1 resulted in a dramatic reduction of in vitro migration, invasion, in vivo liver metastasis of nude mice, which is similar to that occurs with the silencing of miR-107, indicating that DICER1 functions as a metastasis suppressor in gastric cancer. Furthermore, the restoration of DICER1 can inhibit miR-107-induced gastric cancer cell invasion and metastasis. In conclusion, our results suggested that miR-107, an oncogene miRNA promoting gastric cancer metastasis through down-regulation of DICER1. Inhibition of miR-107 or restoration of DICER1 may represent a new potential therapeutic target for gastric cancer treatment.     

胃癌中显著下调的miR-433的作用靶点研究

目的为了筛选胃癌中miRNAs的表达标记,验证胃癌相关miRNAs的作用靶点,建立一种新的诊断和治疗胃癌的方法。方法运用基因芯片技术检测3个正常胃组织标本,24个胃癌组织标本,胃癌细胞SGC7901和正常胃黏膜细胞GES-1中328个miRNAs的表达情况。用以上方法检测出在胃癌组织和SGC7901中,miR-433的表达水平显著下调。为了确保结果的准确性,采用实时荧光定量PCR对其进行验证。并用基因克隆和Western印迹方法分析miR-433的作用靶点。结果共有26个miRNAs在胃癌标本（包括24个胃癌组织和SGC7901）中异常表达。其中19个miRNAs下调,7个miRNAs上调。实时荧光定量PCR检测出miR-433在胃癌标本中的表达水平显著下调,该结果和基因芯片检测结果一致。另外,在本实验中发现miR-433与Grb2（growth factor receptor—bound protein 2）的表达呈负相关。结论胃癌相关miRNAs已进行了初步筛选。其中,miR-433可能是胃癌中的标记性miRNAs之一,Grb2是其作用靶点。这为建立新的以miRNAs为基础的诊断和治疗胃癌的方法提供了相关信息。