MicroRNA-145与肿瘤的关系及研究进展

随着人们对生命科学的认识不断加深,作为非编码RNA的重要代表microRNA受到越来越多的青睐。人类多种肿瘤的发生发展及侵袭转移与microRNAs（miRNAs）存在着密切关系,miRNAs可能成为一类新的致癌基因或抑癌基因,通过抑制靶mRNA翻译或诱导靶mRNA降解在转录后水平调控基因表达,参与肿瘤的发生、发展及侵袭转移。 MiR-145是microRNA家族中的成员之一,被认为是一种肿瘤抑制基因,可以靶向多个肿瘤相关基因,从而影响肿瘤的生长、侵袭转移以及肿瘤血管的生成。并且miR-145可以调控细胞重新编程基因 SOX2、OCT4、KLF4和C-MYC 的表达,由于这些基因也具有癌基因的特性,因此miR-145在肿瘤干细胞中的作用也受到关注。     

microRNA-10b与肿瘤

microRNA-10b(miR-10b)是小分子RNA-microRNAs(miRNAs)的一种,是一类非编码的小分子RNA,在基因转录后的调控中发挥着重要作用。本文miR-10b与多种肿瘤之间不同程度的关系做一综述。     

miR-155在消化道肿瘤中的研究进展

microRNAs(miRNAs)是一种非编码的小分子RNA,调控转录后的基因表达水平。microRNA-155(miR-155)是典型的多功能miRNA,参与了多种生物学过程,包括造血、炎症、免疫和肿瘤等。消化道肿瘤是严重威胁人类生命健康的疾病,近年来研究表明miR-155与消化道肿瘤的发生发展关系密切,在肿瘤的发病机制、诊断、治疗及预后等方面有重要作用。本文就miR-155在消化道肿瘤的研究现状做一综述。     

miR-155在消化道肿瘤中的研究进展

microRNAs（miRNAs）是一种非编码的小分子RNA,调控转录后的基因表达水平。microRNA-155（miR-155）是典型的多功能miRNA,参与了多种生物学过程,包括造血、炎症、免疫和肿瘤等。消化道肿瘤是严重威胁人类生命健康的疾病,近年来研究表明miR-155与消化道肿瘤的发生发展关系密切,在肿瘤的发病机制、诊断、治疗及预后等方面有重要作用。本文就miR-155在消化道肿瘤的研究现状做一综述。     

miR-133a在肿瘤中的研究进展

微小RNA(miRNAs)是一类非编码调控基因,参与调控多种生理病理过程。miR-133a是miRNA的一种。近期研究表明miR-133a在多种肿瘤的发生、发展过程中起重要作用。本文结合近期文献,对miR-133a在肿瘤中的研究进展加以简述。     

MicroRNAs及其在泌尿系肿瘤的研究进展

microRNAs（miRNAs）是一类分布十分广泛的内源性非编码RNA,在动物、植物、病毒中广泛存在。miRNAs与肿瘤的发生发展预后有关,并在肿瘤的增殖、分化及调亡等方面有重要的作用。结合最近相关文献,本文就miRNAs与泌尿系肿瘤方面的进展作简要概述。     

miR-34在肿瘤疾病中的研究进展

肿瘤的发病率和病死率日益增高,严重危害人类身心健康。研究其发生发展的分子调控机制对疾病的诊疗十分重要。微小RNA(miRNA或miR)是一类单链非编码RNA分子,对包括肿瘤在内的各种疾病的进展过程具有重要作用。其中,miR-34是近年来发现的具有肿瘤抑制作用的miRNA。通过多种机制调节基因表达,参与调控细胞的各项生物学行为,抑制多种肿瘤的发生发展。因此miR-34不仅可作为肿瘤预后的生物标志物,也有望成为新的治疗靶点。本文就miR-34在肿瘤疾病中的研究进展进行综述,以期为肿瘤的诊断和治疗提供参考。     

Micro RNA-106b-25簇与肿瘤

Micro RNA(miRNA)是一种由染色体内含子部分编码的,通过降解靶基因的mRNA或抑制其翻译来调控基因表达的小RNA分子,其功能涉及众多的生物学进程,包括增殖、凋亡、发育以及分化等,miRNA的异常表达更是与许多疾病的发生发展相关,如血液肿瘤及实体瘤。miR-106b-25簇micro RNA包括miR-106b、miR-93和miR-25,这些miRNA的功能涉及了肿瘤发生发展等诸多生物进程。该文将就miR-106b-25簇对肿瘤的影响做一综述。     

Notch通路上调miR-223抑制FBXW7表达对结肠癌 HCT116细胞生物学的影响

摘要：目的 探讨microRNAs（miRNAs）对结肠癌HCT116细胞增殖和凋亡的影响及其作用机制。方法 经实时 定量 PCR 和 Western blot 检测 20 例结肠癌组织及癌旁正常组织标本中 FBXW7 mRNA 和其蛋白水平。通过 TargetScan 工具预测、定量 PCR 和荧光素酶活性实验鉴定与 FBXW7 结合的 miRNAs,瞬时转染 miR-223 和其对照 miCtr、抑制剂（Inhibitor）入HCT116细胞后检测FBXW7 mRNA和蛋白水平,CCK-8和流式细胞术分别检测细胞活性 和凋亡率。同时通过 siRNA 下调 Notch3 表达后,检测 miR-223 水平以及细胞凋亡率。结果 结肠肿瘤组织中 FBXW7 mRNA与蛋白含量低于癌旁组织（P＜0.05）,预测并证实miR-223与miR-25能够与FBXW7基因特异结合。 HCT116细胞中瞬时转染miR-223后,FBXW7 mRNA水平和蛋白表达量下调（P＜0.01）,细胞活性增加（P＜0.05）,而 细胞凋亡率降低（P＜0.01）。下调Notch3通路后,miR-223表达水平下降（P＜0.001）,FBXW7 mRNA水平上升（P＜ 0.01）,细胞凋亡率下降（P＜0.05）。结论 Notch通路上调miR-223水平,进而抑制FBXW7基因的表达,最终促进结 肠癌细胞HCT116的增殖并抑制其凋亡。     

MicroRNA作为肿瘤治疗靶点的研究进展

近年研究发现,miRNAs与肿瘤的发生、发展存在着密切的关系。与正常组织相比,肿瘤组织中miRNA的表达谱发生明显的变化,并且miRNA与抑癌基因或原癌基因相互作用,在肿瘤的发生和发展中扮演着重要角色。某些miRNA可具备癌基因的功能,下调抑癌基因的表达,促进了肿瘤的增殖、转移和浸润等;也有一些miRNA具备抑癌基因的功能,下调癌基因的水平,在肿瘤的凋亡、分化和治疗等方面做出了有益的贡献。目前,较多研究已在体内模型中证实靶向致癌miRNA或恢复肿瘤抑制miRNA的治疗方式是非常可行性的。本文将就miRNA作为癌基因或肿瘤抑制基因以及这些miRNA作为肿瘤治疗靶点的最新研究进展作一综述。     

MicroRNAs: small but potent oncogenes or tumor suppressors

MicroRNAs (miRNAs) are small, non-coding RNAs that modulate the expression of target mRNA. Many miRNAs are known to be up- or downregulated in a variety of cancers, suggesting a role for miRNAs in tumorigenesis. The correlation between the expression of miRNAs and their effects on target oncogenes, on tumorigenesis and on the proliferation of cancer cells is beginning to gain experimental evidence. For example, the miRNA (miR)-17-92 cluster has been characterized as an oncogene, while let-7 represses Ras and miR-15a/-16-1 represses Bcl-2, thereby acting as tumor suppressors. Thus, an oncogenic or tumor suppressive miRNA may have potential as a therapeutic target to control cancers. This review will discuss the relationship between miRNAs and tumorigenesis, and the potential for modulating miRNAs for the treatment of cancer.     

Circulating miR-155 expression in plasma: a potential biomarker for early diagnosis of esophageal cancer in humans

MicroRNAs (miRNAs) are postulated to play important roles in oncogenesis. Recently, extracellular miRNAs were detected in plasma or serum of diseased subjects. However, the role of circulating miRNAs in plasma/serum remains to be elucidated. In this study, the relative expressions of miR-155, miR-183, and miR-20a in esophageal tissue were found to be significantly associated with increased risk for esophageal cancer. The relative expressions of circulating miR-155 and miR-183 were significantly reduced in cancer patients. Circulating miR-155 showed significantly higher risk for esophageal cancer when adjusted by smoking status and alcohol use. Circulating miR-155 was found to have significant diagnostic value for esophageal cancer as evidenced by a receiver operating characteristic curve area of 66%. However, Pearson analysis showed no statistical correlation in the relative miRNAs expression between plasma and esophageal tissues, which suggested different origins of circulating miRNAs distinct from tumor cell miRNAs. In conclusion, results suggest that circulating miR-155 in plasma may serve as a reliable, novel, noninvasive biomarker for early diagnosis and detection of esophageal cancer.     

The tumor-suppressive and potential therapeutic functions of miR-34a in epithelial carcinomas

Introduction: Many RNA species have been identified as important players in the development of chronic diseases including cancer. Certain classes of regulatory RNAs such as microRNAs (miRNAs) have been investigated in such detail that bona fide tumor suppressive and oncogenic miRNAs have been identified. Because of this, there has been a major effort to therapeutically target these small RNAs. One in particular, a liposomal formulation of miR-34a (MRX34), has entered Phase I trials.

Areas covered: This review aims to summarize miRNA biology, its regulation within normal versus disease states and how it can be targeted therapeutically, with a particular emphasis on miR-34a. Understanding the complexity of a single miRNA will aid in the development of future RNA-based therapeutics for a broader range of chronic diseases.

Expert opinion: The potential of miRNAs to be developed into anti-cancer therapeutics has become an increasingly important area of research. miR-34a is a tumor suppressive miRNA across many tumor types through its ability to inhibit cellular proliferation, invasion and tumor sphere formation. miR-34a also shows promise within certain in vivo solid tumor models. Finally, as miR-34a moves into clinical trials it will be important to determine if it can further sensitize tumors to certain chemotherapeutic agents.     

Circulating microRNA profiles altered in mice after 28 d exposure to perfluorooctanoic acid

Perfluorooctanoic acid (PFOA) is a stable man-made compound with many industrial and commercial uses. Recently, however, concern has been raised that it may induce various toxicological effects such as hepatotoxicity, immunotoxicity, and developmental toxicity. Because levels of circulating microRNAs (miRNAs) can be altered in several clinical diseases, they may serve as potential novel biomarkers. Here, we explored differences in the profiles of circulating miRNAs in mice after PFOA exposure. Using TaqMan miRNA arrays, we determined that the levels of 24 circulating miRNAs were altered in mice dosed with PFOA at 1.25 mg/kg/d and 73 were altered in mice dosed with 5 mg/kg/d. Eight miRNAs were further validated using TaqMan Real-Time PCR assays. Results were consistent with those obtained from the TaqMan miRNA arrays, except for miR-199a-3p. The most remarkable of the circulating miRNAs (miR-26b-5p and miR-199a-3p) were also up-regulated in the serum of occupational workers in our previous epidemiological study. We also found similar patterns in mice exposed to PFOS. These results demonstrated that circulating miRNA profiles were altered after exposure to high concentrations of PFOA and miR-28-5p, miR-32-5p, miR-122-5p, miR-192-5p, and miR-26b-5p in serum may be linked to effects of PFOA, especially in occupationally exposed people.     

Hyper-methylated miR-203 dysregulates ABL1 and contributes to the nickel-induced tumorigenesis

Nickel compounds have been found to be carcinogenic based upon epidemiological, animal and cell culture studies. Previous studies suggest that epigenetic mechanisms play a role in Nickel-induced carcinogenesis such as DNA methylation and histone modification. In this study, we investigated the role of microRNAs (miRNAs) in nickel-induced carcinogenesis. The expression of several miRNAs which may function as tumor suppressor genes revealed a strong downregulation of miR-203 in Ni₃S₂-transformed 16HBE cells (NSTCs). Meanwhile, we observed hypermethylation of CpGs in miR-203 promoter and first exon area, and proved that the hyper-methylated miR-203 was involved in the Nickel-induced tumorigenesis. Moreover, we identified that miR-203 may suppress the tumorigenesis at least in part through negatively regulating its target gene ABL1. Our findings indicate that DNA methylation-associated silencing of tumor suppressor miRNAs contributes to the development of Nickel-induced cancer.     

MicroRNA delivery by cationic lipoplexes for lung cancer therapy

Lung cancer is the leading cause of cancer deaths in western countries and carries a poor overall five year survival rate. Several studies demonstrate that microRNAs (miRNAs or miRs) are actively involved in tumor development by serving as tumor suppressors, oncogenes or both. In lung cancer, miRNAs may serve as both diagnostic and prognostic biomarkers as well as regulate in vitro and in vivo tumor progression. However, miRNA-based therapy is faced with several challenges including lack of tissue specificity, lack of optimal delivery systems, poor cellular uptake and risk of systemic toxicity. Here, we report a cationic lipid based miRNA delivery system to address some of these challenges. Among many lung cancer related miRNAs, miR-133b, a tumor suppressor, was selected as a therapeutic target because it directly targets the prosurvival gene MCL-1 thus regulating cell survival and sensitivity of lung cancer cells to chemotherapeutic agents. The efficacy of pre-miR-133b containing lipoplexes was evaluated in A549 non-small cell lung cancer (NSCLC) cells. Compared with siPORT NeoFX transfection agent, lipoplexes delivered pre-miR-133b in a more efficient manner with ~2.3-fold increase in mature miR-133b expression and ~1.8-fold difference in MCL-1 protein downregulation in vitro. In the in vivo biodistribution study, lipoplexes achieved ~30% accumulation in lung tissue, which was ~50-fold higher than siPORT NeoFX transfection agent. Mice treated with pre-miR-133b containing lipoplexes had mature miR-133b expression in lung ~52-fold higher than untreated mice. Our results demonstrated that cationic lipoplexes are a promising carrier system for the development of miRNA-based therapeutics in lung cancer treatment.     

miR-27a在妇科肿瘤中的研究进展 #br#

微小 RNA（miRNA）是一类内源性的非编码小 RNA,通常可通过特异性降解 mRNA或抑制蛋白质的翻译, 在转录后水平调控靶基因的表达,参与机体的多个生理或病理过程。miRNA可通过调节癌基因和抑癌基因的表达 来参与肿瘤的发生发展,在不同类型的肿瘤中及肿瘤的不同发展阶段,miRNA分子的表达谱呈现不同的特征。其 中,miR-27a定位于人类 19号染色体,在子宫内膜癌、宫颈癌、卵巢癌等多种妇科肿瘤中异常表达。本文对 miR-27a 在子宫内膜癌、宫颈癌和卵巢癌中的作用及其临床应用进展进行综述,为开发新型的肿瘤分子标志物或靶向药物提 供理论依据。