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。     

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。     

金雀异黄素通过调控miR-27a及其靶基因对卵巢癌细胞SKOV3生长的影响

目的：研究金雀异黄素对卵巢癌细胞株SKOV3生长的抑制作用及其可能的机制。方法：收集卵巢癌组织及良性组织,应用RT-PCR法检测miR-27a的表达。用不同浓度的金雀异黄素处理细胞,通过SRB法检测金雀异黄素单用或加入miR-27amimics后对细胞株生长的抑制作用;经RT-PCR和Western blot检测miR-27a及靶基因Sprouty2表达的变化。结果：miR-27a在卵巢癌组织中的表达高于良性组织（P〈0.05）。金雀异黄素可呈浓度和时间依赖的方式抑制卵巢癌细胞SKOV3生长;金雀异黄素浓度依赖性地下调miR-27a,上调Sprouty2的表达,且miR-27amimics能够部分拮抗金雀异黄素抑制细胞生长的作用。结论：金雀异黄素可能通过下调致癌miR-27a的表达,发挥抑制卵巢癌细胞生长的作用。     

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。     

miR-15a在子宫内膜癌组织中的表达变化及临床意义

目的 探讨miR-15a在子宫内膜癌组织中表达变化及临床意义,分析miR-15a在子宫内膜癌发生发展过程中的可能机制.方法 通过荧光定量PCR法测定68例子宫内膜癌组织和68例癌旁组织的miR-15a表达情况;分别将无关序列模拟物(非转染组)、miR-15a模拟物(转染组)转染入RL95-2人子宫内膜癌细胞,设立阴性对照组,比较3组的miR-15a和基质金属蛋白酶2(MMP-2)表达情况;并通过Transwell肿瘤细胞侵袭试验和Transwell肿瘤细胞迁移试验检测RL95-2细胞的侵袭力和迁移能力.结果 子宫内膜癌组织miR-15a相对表达量明显低于癌旁组织(P<0.05);miR-15a相对表达量与子宫内膜癌患者的FIGO分期、淋巴结转移、肌层浸润程度、分化程度相关(P<0.05);转染组miR-15a相对表达量明显高于未转染组和对照组,MMP-2相对表达量明显低于未转染组和对照组(P<0.05);转染组侵袭力与迁移力均明显低于未转染组和对照组(P<0.05).结论 在子宫内膜癌患者中miR-15a以低表达为主,且与淋巴结转移、分化程度、肌层浸润程度、FIGO分期有关,miR-15a作为抑癌基因可能是通过抑制MMP-2蛋白发挥抑制癌细胞转移及侵袭的作用.     

miRNA 在卵巢癌中作用的研究进展

卵巢癌是目前死亡率最高且预后最差的妇科恶性肿瘤,缺乏有效的早期诊断方法以及化疗耐药是其主要原因。微小RNA（miRNA）是一种内源性的非编码短序列小RNA,主要通过在转录后水平降解靶mRNA或者抑制靶基因的表达而参与调控细胞的生长、增殖和凋亡等。一些miRNA 可以通过调节体内多种癌基因和抑癌基因的表达,参与卵巢癌的发生、浸润及转移等进程;且多种特征性miRNA 在个体内的差异性表达也与卵巢癌的耐药及预后密切相关。研究与卵巢癌相关的miRNA 的作用靶基因及其信号调控通路可为进一步提高卵巢癌的临床诊断与治疗提供新思路。本文主要就miRNA 在卵巢癌中作用的研究进展进行综述。     

高级别浆液型卵巢癌中微RNA 18a-5p糖类抗原-125人附睾蛋白4表达及其意义

<正>卵巢恶性肿瘤是妇科常见的三大恶性肿瘤之一,其发病率位居子宫颈癌及子宫内膜癌后的第三位,致死率却居首位~([1])。由于卵巢在盆腔较深位置,一般不易扪及,且早期没有明显症状;在临床上患者如果有腹胀、腹部肿块或腹腔积液等表现,显示肿瘤已长大或到晚期。数据表明早期卵巢癌患者的5年存活率可高达85%以上,晚期患者不足30%[2]。其中高级别浆液型卵巢癌(HGSOC)是卵巢癌患者死亡的最主要原因,所占比例达70%～80%,且病死率居高不下~([2])。微RNAs(miRNA)是一类在体内有多种生理功能,可调控基因表达,长度约为22个核苷酸的非编码单链RNA。miRNA在体内作为指引分子,通过和mRNA分子的碱基配     

下调miR-374a通过靶向TCF21抑制宫颈癌细胞SiHa增殖、迁移、侵袭的分子机制

摘要：目的:阐明下调miR-374a靶向转录因子21（TCF21）调控宫颈癌细胞增殖、迁移、侵袭的分子机制。方法:采用Realtime PCR法检测微小RNA（miR）-374a在正常宫颈上皮细胞和宫颈癌细胞中的表达变化。在宫颈癌细胞Si Ha中转染miR-374a inhibitor,MTT检测细胞增殖,Transwell小室检测细胞侵袭以及迁移能力变化,Western blot检测细胞中基质金属蛋白酶2（MMP-2）、基质金属蛋白酶9（MMP-9）蛋白表达变化。在线靶基因预测软件预测miR-374a的靶基因可能为TCF21,荧光素酶报告系统鉴定靶向关系。在宫颈癌细胞Si Ha中共转染miR-374a inhibitor和TCF21 siRNA,检测细胞增殖、侵袭、迁移变化。结果:miR-374a在正常宫颈上皮细胞中的表达水平明显低于宫颈癌细胞。转染miR-374a inhibitor后的宫颈癌细胞Si Ha增殖、迁移和侵袭能力下降,细胞中MMP-2和MMP-9蛋白表达减少。miR-374a靶向负调控TCF21表达。TCF21 siRNA逆转miR-374a inhibitor对宫颈癌细胞Si Ha增殖、侵袭和迁移的抑制作用。结论:下调miR-374a通过靶向TCF21抑制宫颈癌细胞Si Ha增殖、迁移、侵袭。     

微小 RNA-338-3p靶向调控高迁移率族蛋白 B1增强子宫内膜癌对紫杉醇敏感性的研究

目的 探讨miR-338-3p靶向调控高迁移率族蛋白B1(HMGB1)影响子宫内膜癌对紫杉醇(Paclitaxel,PTX)敏感性的分子机制.方法 实时荧光定量聚合酶链反应(qRT-PCR)和蛋白印迹法(Western blottingting)检测miR-338-3p和HMGB1在子宫内膜癌细胞Ishikawa和HEC-1B中的表达;双荧光素酶报告基因实验验证miR-338-3p和HMGB1之间的靶向关系;将Ishikawa和HEC-1B细胞分为如下5组:miR-338-3p组(转染miR-338-3p mimics组)、miR-NC组(转染miRNA阴性对照组)、si-HMGB1组(转染干扰RNA)、si-NC组(转染siRNA阴性对照)、miR-338-3p+HMGB1组(共转染miR-338-3pmimics和pcDNA3.0 HMGB1组).将各组用转染试剂转染至细胞,用不同浓度的PTX处理上述转染组细胞,CCK-8法检测Ishikawa和HEC-1B细胞增殖,Annexin V-FITC/PI检测细胞凋亡,Western blotting检测HMGBI蛋白表达.结果 与人正常子宫内膜上皮细胞ESC相比,miR-338-3p在子宫内膜癌细胞Ishikawa和HEC-1B中表达下调[(1.00±0.10)比(0.51±0.04)、(0.46±0.04)],而HMGB1则相反;miR-338-3p靶向并负性调节HMGB1表达;过表达miR-338-3p抑制子宫内膜癌细胞Ishikawa和HEC-1B增殖,促进凋亡,增加其对PTX敏感,与敲低HMGB1结果一致;HMGB1可部分逆转miR-338-3p对子宫内膜癌细胞增殖,凋亡以及对PTX敏感性的影响.结论 miR-338-3p通过负性调控HMGB1抑制子宫内膜癌细胞Ishikawa和HEC-1B增殖,促进凋亡和增强其对PTX敏感性.     

MicroRNA-21表达调控研究

MicroRNAs(miRNAs)是一类广泛存在于真核细胞中的长约22 nt的非蛋白编码的、单链RNA,具有转录后基因调控的功能,与细胞分化、生长以及代谢等多种生物学过程的调节有关。研究发现,人体很多肿瘤中都存在miRNA的差异表达。而在这些差异表达的miRNA中,又以miR-21(miRNA-21)较为特殊。因为miR-21在几乎所有实体肿瘤中都存在高表达,而且高表达的miR-21可能发挥类似原癌基因的作用。miR-21通过负调节靶基因增加肿瘤细胞的增殖、凋亡以及肿瘤侵入转移,这些靶基因有PTEN、PDCD4、RECK等等。该文主要介绍miR-21在肿瘤中的作用、调节机制,以及作为靶基因在肿瘤的治疗中的临床意义。     

miRNA: small molecules as potential novel biomarkers in cancer

Four different types of small RNAs functionally associated with gene silencing have been discovered in animals including small interfering RNAs (siRNAs), microRNAs (miRNAs), and Piwi-interacting RNAs (piRNAs). Experimental evidence suggests that miRNAs regulate the expression of more than 30% of protein-coding genes. These molecules can also act as oncogenes or tumor suppressors. Expression profiling has revealed characteristic miRNA signatures not only in human cancers but also in serum and blood cells of cancer patients. Numerous human miRNA genes map to chromosomal regions which are susceptible to amplification, deletion or translocation in the process of tumor development. Despite the pivotal role of miRNA in cancer precise mechanisms of action are yet to be elucidated. This review is focused on recent findings related to the emerging field of miRNA serving as novel potential biomarkers in cancer diagnosis, prognosis and possibly, therapies.     

MicroRNA expression is differentially altered by xenobiotic drugs in different human cell lines

Several noncoding microRNAs (miR or miRNA) have been shown to regulate the expression of drug-metabolizing enzymes and transporters. Xenobiotic drug-induced changes in enzyme and transporter expression may be associated with the alteration of miRNA expression. Therefore, this study investigated the impact of 19 xenobiotic drugs (e.g. dexamethasone, vinblastine, bilobalide and cocaine) on the expression of ten miRNAs (miR-18a, -27a, -27b, -124a, -148a, -324-3p, -328, -451, -519c and -1291) in MCF-7, Caco-2, SH-SY5Y and BE(2)-M17 cell systems. The data revealed that miRNAs were differentially expressed in human cell lines and the change in miRNA expression was dependent on the drug, as well as the type of cells investigated. Notably, treatment with bilobalide led to a 10-fold increase of miR-27a and a 2-fold decrease of miR-148a in Caco-2 cells, but no change of miR-27a and a 2-fold increase of miR-148a in MCF-7 cells. Neuronal miR-124a was generally down-regulated by psychoactive drugs (e.g. cocaine, methadone and fluoxetine) in BE(2)-M17 and SH-SY5Y cells. Dexamethasone and vinblastine, inducers of drug-metabolizing enzymes and transporters, suppressed the expression of miR-27b, -148a and -451 that down-regulate the enzymes and transporters. These findings should provide increased understanding of the altered gene expression underlying drug disposition, multidrug resistance, drug-drug interactions and neuroplasticity.     

The role of miR-506 in transformed 16HBE cells induced by anti-benzo[a]pyrene-trans-7,8-dihydrodiol-9,10-epoxide

Growing evidence indicates that the alteration of microRNA (miRNA) expression in tumors that is induced by chemical carcinogens plays an important role in tumor development and progression. However, the mechanism underlying miRNA involvement in lung carcinogenesis induced by anti-benzo[a]pyrene-trans-7,8-dihydrodiol-9,10-epoxide (anti-BPDE) remains unclear. In our study, we used the malignant transformation of human bronchial epithelial cells (16HBE-T) induced by anti-BPDE to explore the mechanisms of human lung carcinogenesis. We found that expression of miR-506 was reduced in 16HBE-T transformed malignant human bronchial epithelial cells compared with 16HBE normal human bronchial epithelial cells. Restoration of miR-506 in 16HBE-T cells led to a decrease in cell proliferation, G0/G1 phase cell cycle arrest, as well as significantly suppressed anchorage-dependent growth in vitro and tumor growth inhibition in a nude mouse xenograft model. In addition, we provided novel evidence regarding the role miR-506 potentially plays in negatively regulating the protein and mRNA expression level of N-Ras in cancer cells. Together, these findings revealed that miR-506 acts as an anti-oncogenic miRNA (anti-oncomir) in malignantly transformed cells. The identification of tumor suppressive miRNAs could provide new insight into the molecular mechanisms of chemical carcinogenesis.     

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.