MicroRNA与肺癌的关系研究进展.docx
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microRNA与肺癌的关系研究进展胡亚峰按照稿约填写你的资料、单位、地址、电话等。“北京医学”要求3500字,你看完把意见给我,我再改改。引言自2003年Ambros等首次在线虫中发现首个microRNAlin-4,并发现其时序性调控线虫发育的功能后,众多的研究者对这一新的调控分子进行了广泛而深入的研究,发现了多个microRNA。作为非编码RNA的成员,成熟microRNA是一类长度2123核苷酸的内源调控性小RNA分子,通过与靶基因的3非编码区(3UTR)互补结合,以对靶mRNA剪切和抑制蛋白质翻译的方式负性调控靶基因。目前已知microRNA可以调节约50%的蛋白编码基因,包括发育、分化和凋亡等生理过程和炎症、肿瘤、心血管疾病等病理过程均有microRNA的参与。在所有肿瘤之中,肺癌的死亡率居首位。尽管有关肺癌的早期诊断技术、化疗和靶向治疗不断革新,肺癌的5年存活率依旧较低,复发率较高。对肺癌生物学有限的了解是影响其预后的主要原因。近年出现的microRNA与肺癌关系的研究丰富了对肺癌发生、发展等机理的认识,为肺癌早期诊断、基因药物的研发和判断预后提供了可靠的理论基础。本文对microRNA与肺癌的关系进行了综述。1 microRNA概述microRNA是一类长度为2023核苷酸的非编码RNA分子,存在于多种生物的基因组中,在转录后水平以序列特异性调节的方式调控基因表达。成熟microRNA的形成包含以下步骤:microRNA基因由RNase转录为pri-microRNA的初级转录产物,在细胞核内由称为Drosha的RNase对其进行第一次剪切成为带有茎-环结构的长约70个核苷酸的microRNA前体pre-microRNA,随后在细胞浆中由Dicer酶催化其第二次剪切形成成熟microRNA。其中还有若干重要蛋白、因子,如DGCR8蛋白、Exportin5因子等的辅助才可准确生成成熟microRNA。成熟microRNA选择性整合入RNA诱导的沉默复合物(RNA induced silencing complex,RISC)中识别靶基因,其与靶基因完全互补时会引发靶mRNA的降解,与靶基因互补程度较低时引起mRNA翻译的抑制。microRNA及其调控的靶基因的表达构成一个调控网络,动态调控生物体各种生物学过程的运行。通过杂交、聚合酶链反应及基因芯片等方法检测microRNA在不同生理、病理状况下的表达状况,于体内、外水平对差异microRNA进行过表达和抑制表达以观察组织、细胞等表型变化,利用生物信息学分析结合报告基因系统及其他分子生物学技术进行验证成为microRNA研究的主要策略。由于作用机制的特殊性,使得单个microRNA可以调控多个靶基因或多个microRNA共同调控同一靶基因存在可能,因此经过确认的microRNA-靶基因配对仅揭示microRNA调控网络的一部分。2 microRNA通过调控不同的靶基因在肺癌发生过程中所发挥的功能 肺癌是严重危害人类健康的恶性肿瘤之一,死亡率很高。其发生机制复杂,目前尚未完全明确。作为生物体重要的一类调控分子,microRNA在肺癌中存在失控表达。自let-7簇被发现差异表达并且在肺癌发生、发展具有重要功能以来,microRNA引起人们极大兴趣,多个研究小组对与肺癌密切相关的众多microRNA进行了研究,对其靶基因和功能有了基本的了解。我们选取若干具有特征性的microRNA进行综述。2.1 let-7簇let-7簇最早发现于线虫,与分化、发育密切相关。人let-7序列与线虫高度保守,有多个成员,某些成员的基因恰位于肿瘤缺失的基因区域。Takamizawa 1等最先利用Northern Blot检测多个肺癌细胞系及143例非小细胞肺癌(nonsmall cell lung carcinoma,NSCLC)的治疗性切除标本中let-7簇的表达,发现60%细胞系中let-7簇的低表达,44%临床标本中let-7簇表达水平下降80%,对肺癌病人进行5年随访发现,除肺癌分期外,let-7簇各亚型的低表达是影响肺癌切除病人存活率的独立预测因子,此外,在A549肺腺癌细胞系过表达Let-7抑制了肺癌细胞的生长。let-7簇的靶基因众多,包括RAS, HMGA2, IMP-1等(表1)。作为肺癌重要的原癌基因,RAS基因产物通过调控基因转录激酶进而调节细胞生长和分化,其突变是众多肿瘤发生的原因。let-7簇通过与N-RAS和K-RAS的mRNA3UTR互补结合调控RAS表达,肺癌组织let-7簇的低表达解除了对RAS的负调控进而导致肿瘤发生2。HMGA是非组蛋白的染色体蛋白的重要成员,参与分化和发育相关的转录调控,HMGA2通过引起染色质易位而导致肿瘤发生。Kumar 3等发现过表达let-7簇的NSCLC细胞周期停滞和死亡,肿瘤细胞异位移植于过表达let-7簇小鼠表现出肿瘤的生长抑制,NSCLC细胞生长抑制主要是let-7带来的HMGA2降低引起。目前已经证实的let-7簇靶基因还有很多,这些已经确定的let-7簇-靶基因配对明确了let-7簇的肿瘤抑制作用。1.2 mir-17-92簇mir-17-92簇包含多个成员,位于C13orf25基因的内含子区域,成熟mir-17-92簇过表达于肺癌组织,特别是小细胞肺癌(small cell lung carcinoma,SLC)。对NSCLS细胞进行包括mir-17-5p和mir-20a的mir-17-92簇反义寡核苷酸处理降低了它们的表达,引起显著的凋亡效应,进一步功能研究发现缺氧诱导因子(HIF)-1mir-17-92簇的靶基因表达升高是引起凋亡的原因。HIF-1是氧依赖的转录因子的一种,具有转录激活某些与凋亡、代谢、增殖和侵袭等基因的作用。而且,癌基因c-myc可以通过结合于C13orf25基因的启动子区域转录激活mir-17-92簇,表达增高的mir-17-92簇引起HIF-1的降低,进而引起凋亡抑制、细胞周期停滞失效等作用,而引起肿瘤发生4。1.3 mir-34上皮-间充质转化(EMT)是上皮细胞在某些通路作用下转换为具有间质表型的细胞的过程,是上皮来源的恶性肿瘤获得迁移及侵袭能力的重要生物学过程。Snail1作为一种锌指蛋白转录抑制子,其异常表达与EMT过程密切相关。在肺腺癌细胞,当抗癌基因p53突变或失去功能时,失去抑制的Snail1会引发EMT,其原因是mir-34表达水平的降低。mir-34的靶基因不仅包括Snail1,还有Snail1的调控分子如:-catenin、LEF1等5,这凸显了mir-34在P53基因突变的肺癌侵袭和转移中的作用。CyclinE是细胞周期素依赖激酶CDK2的一个正相调节亚单位,CyclinE作为mir-34c的靶基因,与包括肺癌等多种肿瘤的发生发展相关6。2.4 表皮生长因子EGFR与microRNAEGFR作为erbB受体家族成员之一,广泛表达于人类各个组织,调控包括增值、分化和发育等细胞过程。EGFR信号通路的异常是发生上皮来源肿瘤的重要原因。包括mir-21和mir-125a-5p的一些microRNA作为此通路的下游调控分子,在肺癌发生过程发挥重要作用。肺癌细胞中磷酸化的EGFR导致mir-21的高表达,EGFR抑制剂显著降低mir-21的表达,mir-21的反义寡核苷酸处理突变型肺腺癌细胞会增强EGFR抑制剂诱导的凋亡作用,处理野生型肺腺癌细胞时mir-21本身就可诱导肺癌细胞的凋亡7,这些结果凸显了mir-21在EGFR突变型及野生型肺癌中潜在药物靶点的作用。同样,mir-125a-5p具有抑制肺癌侵袭和转移的作用,肺癌组织EGFR通路的mir-125a-5p的低表达与肺癌发生密切相关 8。2.5 microRNA与单核苷酸多态性单核苷酸多态性(single nucleotide polymorphism,SNP)是指不同个体基因在某一特定核苷酸位置存在单个不同碱基的现象,且其频率至少大于1%。SNP不均匀分布于基因组中,在非编码序列的分布远多于蛋白编码序列。发生在pre-microRNA的SNP将会改变成熟microRNA的加工、表达和与靶基因的结合,如此导致对某些肿瘤的易感性或侵袭性的改变。Hu9等人发现miR-196a2的SNP(re11614913)与NSCLC的存活率紧密相关,此位点上是纯合子CC的病人存活率显著降低,对miR-196a2与其包括KIF20A、DHFR等靶基因结合实验发现SNP影响其与靶基因的集合。随后进行的对照研究10发现纯合子CC相比于纯合子TT及杂合子TC,具有显著增加肺癌发生的风险。2.6 肺癌耐药相关microRNASCLC占所有肺癌的15%,尽管对放化敏感,部分病人依旧由于药物抵抗而癌症复发或预后不良。癌症病人对药物抵抗的机理十分复杂,包括药物本身的转运、代谢,DNA合成及修复等。具有转录后调控机制的microRNA通过多种机制参与肺癌的耐药。Guo11等通过microRNA芯片和cDNA芯片比较化疗敏感NCI-H69及不敏感NCL-H69AR细胞系(SCLC)在阿霉素作用下microRNA和mRNA表达谱的变化,通过两者的负相关关系,确定与药物抵抗相关的microRNA群,对具有显著性差异的mir-134簇(包括mir-134/379/495等)进行功能分析发现:mir-134的靶基因是具有药物抵抗作用的转膜糖蛋白MRP1/ABCC1,并且具有使细胞周期停滞于G1期的作用,mir-134在肺癌当中的下调准确解释了NCL-H69AR细胞系耐药的原因。Ranade12等通过观察SCLC标本microRNA表达状况并与与临床结合观察耐药与预后的关系发现:mir-92a-2与化疗耐药紧密相关,只有性别和mir-92a-2高表达与生存率相关,由此揭示了mir-92a-2与肺癌耐药的关系。2.7 血清microRNA与肺癌2008年,Chen发现血清中存在稳定的成熟microRNA,这些microRNA十分稳定,可以抵抗RNA酶的消化。通过测序技术并在肺癌病人和正常对照组进行PCR验证发现mir-25和mir-223在血清中存在特异表达。Hu13等通过比较60个具有不同生存期的NSCLC病人血清microRNA表达并在243个病人中验证发现包括mir-486,mir-30d,mir-1和mir-499与NSCLC病人总生存率密切相关。类似地,Foss14等通过对早期NSCLC病人与正常对照组血清microRNA进行比较分析发现mir-1254和mir-574-5p在肺癌病人血清中显著增高,进行验证发现这两个microRNA分别有73%和71%的敏感性和特异性。在血清中microRNA的来源及其释放入血的机制至今尚未完全阐明。来源于肺癌组织的微粒体可能是血清microRNA的来源。某些microRNA在微粒体以远高于肺癌细胞的浓度存在暗示了microRNA的来源可能是肺癌组织。但是肺癌组织异常表达的let-7家族、mir-137等并未在血清中观察到异常表达。这些microRNA的血清选择性表达机制不明。3 microRNA在肺癌研究中的分析与展望异常表达的microRNA在肺癌发生、发展中具有重要调控作用,提示它在肺癌临床各个方面具有很大的潜能。高质量CT的不普及和一定的误诊率等原因是导致肺癌的早期诊断率很低的原因。microRNA在外周血、痰液和呼出气的稳定存在和高质量microRNA的检测方法使得microRNA有希望成为很好的早期诊断指标。治疗方面,肺癌发生、发展关键步骤存在microRNA的调控既是将来新的药物靶点的研究方向、耐药相关microRNA的确定又使得优化已有的药物成为可能。在判断预后方面,一些研究也确定了有一定特异性和敏感度的预后相关microRNA。尽管现有的实验研究存在样本偏少、对照组选择值得商榷和microRNA作用机制的特殊性使得对它的揭示存在部分性和片面性等原因,microRNA的关键调控作用必定会成为解决肺癌甚至其他疾病的关键。Table 1 microRNA于肺癌组织及细胞系的表达状况及其功能microRNA表达来源靶基因功能参考文献Let-7簇NS, BACRAS, HMGA2, IMP-1, c-myc影响细胞周期,细胞分裂、增殖1-3, 15-17mir-17-92簇NSHIF-1, -H2AX发育,抑制凋亡、DNA损伤4, 18-21mir-155NSFOXO3A 放疗保护15, 22mir-34NSCyclinE, Snail1凋亡,抑制EMT5, 6, 23, 24mir-29NSDNMT3a/3b抑制肿瘤侵袭、增殖25, 26mir-200NSTCF8, RAB14抑制EMT27-29mir-126NSCrk, CYP2A, VEGF-A, EGFL7抑制粘附、迁移、侵袭30-33mir-221, 222NS, LKit, p27kip1凋亡抑制34-36mir-21NSPdcd4, Spry1/2, Btg2, Apaf1, Faslg, RhoB, PTEN凋亡抑制7, 31, 37-40mir-1BECMET, Pim-1, FoxP1, HDAC4抑制肿瘤生长、复制41mir-183NSEzrin抑制迁移、侵袭31, 42mir-128NSEGFR抑制增殖31, 43mir-137/372/182NSN/A预后相关,侵袭?36mir-15a/16NSG1cyclins细胞周期转换44mir-133BNSMCL-1, BCL2L2凋亡45mir-93/98/197SC, NSFus1促进肿瘤生成46mir-7NSEGFR, Raf1抑制细胞周期、生长和细胞活力47mir-145NSc-myc, EGFR, NUDT1, OCT4抑制细胞增殖48-50mir-212NSPED, PTCH1凋亡51, 52mir-182NSRGS17, CTTN抑制增殖53, 54mir-218NSPXN抑制增殖、迁移55mir-155NSApaf-1, FOXO3A介导顺铂和放射治疗耐受22, 56mir-375NSYAP1ASH1介导的神经内分泌肿瘤57NS,非小细胞肺癌;SC,小细胞肺癌,BAC,细支气管肺泡癌;BEC,支气管上皮细胞;L,平滑肌肉瘤;EMT,上皮间质转换;N/A,未提及。参考文献1 Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, et al. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer research. 2004;64:3753-6.2 Inamura K, Togashi Y, Nomura K, Ninomiya H, Hiramatsu M, Satoh Y, et al. let-7 microRNA expression is reduced in bronchioloalveolar carcinoma, a non-invasive carcinoma, and is not correlated with prognosis. Lung cancer (Amsterdam, Netherlands). 2007;58:392-6.3 Kumar MS, Erkeland SJ, Pester RE, Chen CY, Ebert MS, Sharp PA, et al. Suppression of non-small cell lung tumor development by the let-7 microRNA family. Proceedings of the National Academy of Sciences of the United States of America. 2008;105:3903-8.4 Taguchi A, Yanagisawa K, Tanaka M, Cao K, Matsuyama Y, Goto H, et al. Identification of hypoxia-inducible factor-1 alpha as a novel target for miR-17-92 microRNA cluster. Cancer research. 2008;68:5540-5.5 Kim NH, Kim HS, Li XY, Lee I, Choi HS, Kang SE, et al. A p53/miRNA-34 axis regulates Snail1-dependent cancer cell epithelial-mesenchymal transition. The Journal of cell biology. 2011;195:417-33.6 Liu X, Sempere LF, Galimberti F, Freemantle SJ, Black C, Dragnev KH, et al. Uncovering growth-suppressive MicroRNAs in lung cancer. Clinical cancer research : an official journal of the American Association for Cancer Research. 2009;15:1177-83.7 Seike M, Goto A, Okano T, Bowman ED, Schetter AJ, Horikawa I, et al. MiR-21 is an EGFR-regulated anti-apoptotic factor in lung cancer in never-smokers. Proceedings of the National Academy of Sciences of the United States of America. 2009;106:12085-90.8 Wang G, Mao W, Zheng S, Ye J. Epidermal growth factor receptor-regulated miR-125a-5p-a metastatic inhibitor of lung cancer. The FEBS journal. 2009;276:5571-8.9 Hu Z, Chen J, Tian T, Zhou X, Gu H, Xu L, et al. Genetic variants of miRNA sequences and non-small cell lung cancer survival. The Journal of clinical investigation. 2008;118:2600-8.10 Tian T, Shu Y, Chen J, Hu Z, Xu L, Jin G, et al. A functional genetic variant in microRNA-196a2 is associated with increased susceptibility of lung cancer in Chinese. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2009;18:1183-7.11 Guo L, Liu Y, Bai Y, Sun Y, Xiao F, Guo Y. Gene expression profiling of drug-resistant small cell lung cancer cells by combining microRNA and cDNA expression analysis. European journal of cancer (Oxford, England : 1990). 2010;46:1692-702.12 Ranade AR, Cherba D, Sridhar S, Richardson P, Webb C, Paripati A, et al. MicroRNA 92a-2*: a biomarker predictive for chemoresistance and prognostic for survival in patients with small cell lung cancer. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2010;5:1273-8.13 Hu Z, Chen X, Zhao Y, Tian T, Jin G, Shu Y, et al. Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2010;28:1721-6.14 Foss KM, Sima C, Ugolini D, Neri M, Allen KE, Weiss GJ. miR-1254 and miR-574-5p: serum-based microRNA biomarkers for early-stage non-small cell lung cancer. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2011;6:482-8.15 Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer cell. 2006;9:189-98.16 Johnson CD, Esquela-Kerscher A, Stefani G, Byrom M, Kelnar K, Ovcharenko D, et al. The let-7 microRNA represses cell proliferation pathways in human cells. Cancer research. 2007;67:7713-22.17 Esquela-Kerscher A, Trang P, Wiggins JF, Patrawala L, Cheng A, Ford L, et al. The let-7 microRNA reduces tumor growth in mouse models of lung cancer. Cell cycle (Georgetown, Tex). 2008;7:759-64.18 Hayashita Y, Osada H, Tatematsu Y, Yamada H, Yanagisawa K, Tomida S, et al. A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer research. 2005;65:9628-32.19 Ventura A, Young AG, Winslow MM, Lintault L, Meissner A, Erkeland SJ, et al. Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell. 2008;132:875-86.20 Matsubara H, Takeuchi T, Nishikawa E, Yanagisawa K, Hayashita Y, Ebi H, et al. Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92. Oncogene. 2007;26:6099-105.21 Ebi H, Sato T, Sugito N, Hosono Y, Yatabe Y, Matsuyama Y, et al. Counterbalance between RB inactivation and miR-17-92 overexpression in reactive oxygen species and DNA damage induction in lung cancers. Oncogene. 2009;28:3371-9.22 Babar IA, Czochor J, Steinmetz A, Weidhaas JB, Glazer PM, Slack FJ. Inhibition of hypoxia-induced miR-155 radiosensitizes hypoxic lung cancer cells. Cancer biology & therapy. 2011;12:908-14.23 Gallardo E, Navarro A, Vinolas N, Marrades RM, Diaz T, Gel B, et al. miR-34a as a prognostic marker of relapse in surgically resected non-small-cell lung cancer. Carcinogenesis. 2009;30:1903-9.24 Mascaux C, Laes JF, Anthoine G, Haller A, Ninane V, Burny A, et al. Evolution of microRNA expression during human bronchial squamous carcinogenesis. The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology. 2009;33:352-9.25 Fabbri M, Garzon R, Cimmino A, Liu Z, Zanesi N, Callegari E, et al. MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proceedings of the National Academy of Sciences of the United States of America. 2007;104:15805-10.26 Muniyappa MK, Dowling P, Henry M, Meleady P, Doolan P, Gammell P, et al. MiRNA-29a regulates the expression of numerous proteins and reduces the invasiveness and proliferation of human carcinoma cell lines. European journal of cancer (Oxford, England : 1990). 2009;45:3104-18.27 Hurteau GJ, Carlson JA, Spivack SD, Brock GJ. Overexpression of the microRNA hsa-miR-200c leads to reduced expression of transcription factor 8 and increased expression of E-cadherin. Cancer research. 2007;67:7972-6.28 Ceppi P, Mudduluru G, Kumarswamy R, Rapa I, Scagliotti GV, Papotti M, et al. Loss of miR-200c expression induces an aggressive, invasive, and chemoresistant phenotype in non-small cell lung cancer. Molecular cancer research : MCR. 2010;8:1207-16.29 Kanzaki H, Ito S, Hanafusa H, Jitsumori Y, Tamaru S, Shimizu K, et al. Identification of direct targets for the miR-17-92 cluster by proteomic analysis. Proteomics. 2011;11:3531-9.30 Kalscheuer S, Zhang X, Zeng Y, Upadhyaya P. Differential expression of microRNAs in early-stage neoplastic transformation in the lungs of F344 rats chronically treated with the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Carcinogenesis. 2008;29:2394-9.31 Cho WC, Chow AS, Au JS. Restoration of tumour suppressor hsa-miR-145 inhibits cancer cell growth in lung adenocarcinoma patients with epidermal growth factor receptor mutation. European journal of cancer (Oxford, England : 1990). 2009;45:2197-206.32 Liu B, Peng XC, Zheng XL, Wang J, Qin YW. MiR-126 restoration down-regulate VEGF and inhibit the growth of lung cancer cell lines in vitro and in vivo. Lung cancer (Amsterdam, Netherlands). 2009;66:169-75.33 Sun Y, Bai Y, Zhang F, Wang Y, Guo Y, Guo L. miR-126 inhibits non-small cell lung cancer cells proliferation by targeting EGFL7. Biochemical and biophysical research communications. 2010;391:1483-9.34 Garofalo M, Quintavalle C, Di Leva G, Zanca C, Romano G, Taccioli C, et al. MicroRNA signatures of TRAIL resistance in human non-small cell lung cancer. Oncogene. 2008;27:3845-55.35 Nuovo GJ, Schmittgen TD. Benign metastasizing leiomyoma of the lung: clinicopathologic, immunohistochemical, and micro-RNA analyses. Diagnostic molecular pathology : the American journal of surgical pathology, part B. 2008;17:145-50.36 Yu SL, Chen HY, Chang GC, Chen CY, Chen HW, Singh S, et al. MicroRNA signature predicts survival and relapse in lung cancer. Cancer cell. 2008;13:48-57.37 Lu Z, Liu M, Stribinskis V, Klinge CM, Ramos KS, Colburn NH, et al. MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene. Oncogene. 2008;27:4373-9.38 Markou A, Tsaroucha EG, Kaklamanis L, Fotinou M, Georgoulias V, Lianidou ES. Prognostic value of mature microRNA-21 and microRNA-205 overexpression in non-small cell lung cancer by quantitative real-time RT-PCR. Clinical chemistry. 2008;54:1696-704.39 Zhu S, Wu H, Wu F, Nie D, Sheng S, Mo YY. MicroRNA-21 targets tumor suppressor genes in invasion and metastasis. Cell research. 2008;18:350-9.40 Hatley ME, Patrick DM, Garcia MR, Richardson JA, Bassel-Duby R, van Rooij E, et al. Modulation of K-Ras-dependent lung tumorigenesis by MicroRNA-21. Cancer cell. 2010;18:282-93.41 Nasser MW, Datta J, Nuovo G, Kutay H, Motiwala T, Majumder S, et al. Down-regulation of micro-RNA-1 (miR-1) in lung cancer. Suppression of tumorigenic property of lung cancer cells and their sensitization to doxorubicin-induced apoptosis by miR-1. The Journal of biological chemistry. 2008;283:33394-405.42 Wang G, Mao W, Zheng S. MicroRNA-183 regulates Ezrin expression in lung cancer cells. FEBS letters. 2008;582:3663-8.43 Weiss GJ, Bemis LT, Nakajima E, Sugita M, Birks DK, Robinson WA, et al. EGFR regulation by microRNA in lung cancer: correlation with clinical response and survival to gefitinib and EGFR expression in cell lines. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2008;19:1053-9.44 Bandi N, Zbinden S, Gugger M, Arnold M, Kocher V, Hasan L, et al. miR-15a and miR-16 are implicated in cell cycle regulation in a Rb-dependent manner and are frequently deleted or down-regulated in non-small cell lung cancer. Cancer research. 2009;69:5553-9.45 Crawford M, Batte K, Yu L, Wu X, Nuovo GJ, Marsh CB, et al. MicroRNA 133B targets pro-survival molecules MCL-1 and BCL2L2 in lung cancer. Biochemical and biophysical research communications. 2009;388:483-9.46 Du L, Schageman JJ, Subauste MC, Saber B, Hammond SM, Prudkin L, et al. miR-93, miR-98, and miR-197 regulate expression of tumor suppressor gene FUS1. Molecular cancer research : MCR. 2009;7:1234-43.47 Webster RJ, Giles KM, Price KJ, Zhang PM, Mattick JS, Leedman PJ. Regulation of epidermal growth factor receptor signaling in human cancer cells by microRNA-7. The Journal of biological chemistry. 2009;284:5731-41.48 Chen Z, Zeng H, Guo Y, Liu P, Pan H, Deng A, et al. miRNA-145 inhibits non-small cell lung cancer cell proliferation by targeting c-Myc. Journal of experimental & clinical cancer research : CR. 2010;29:151.49 Cho WC, Chow AS, Au JS. MiR-145 inhibits cell proliferation of human lung adenocarcinoma by targeting EGFR and NUDT1. RNA biology. 2011;8:125-31.50 Yin R, Zhang S, Wu Y, Fan X, Jiang F, Zhang Z, et al. microRNA-145 suppresses lung adenocarcinoma-initiating cell proliferation by targeting OCT4. Oncology reports. 2011;25:1747-54.51 Incoronato M, Garofalo M, Urso L, Romano G, Quintavalle C, Zanca C, et al. miR-212 increases tumor necrosis factor-related apoptosis-inducing ligand sensitivity in non-small cell lung cancer by targeting the antiapoptotic protein PED. Cancer research. 2010;70:3638-46.52 Li Y, Zhang D, Chen C, Ruan Z, Huang Y. MicroRNA-212 displays tumor-promoting properties in non-small cell lung cancer cells and targets the hedgehog pathway receptor PTCH1. Molecular biology of the cell. 2012;23:1423-34.53 Sun Y, Fang R, Li C, Li L, Li F, Ye X, et al. Hsa-mir-182 suppresses lung tumorigenesis through down regulation of RGS17 expression in vitro. Biochemical and biophysical research communications. 2010;396:501-7.54 Zhang L, Liu T, Huang Y, Liu J. microRNA-182 inhibits the proliferation and invasion of human lung adenocarcinoma cells through its effect on human cortical actin-associated protein. International journal of molecular medicine. 2011;28:381-8.55 Wu DW, Cheng YW, Wang J, Chen CY, Lee H. Paxillin predicts survival and relapse in non-small cell lung cancer by microRNA-218 targeting. Cancer research. 2010;70:10392-401.56 Zang YS, Zhong YF, Fang Z, Li B, An J. MiR-155 inhibits the sensitivity of lung cancer cells to cisplatin via negative regulation of Apaf-1 expression. Cancer gene therapy. 2012;19:773-8.57 Nishikawa E, Osada H, Okazaki Y, Arima C, Tomida S, Tatematsu Y, et al. miR-375 is activated by ASH1 and inhibits YAP1 in a lineage-dependent manner in lung cancer. Cancer research. 2011;71:6165-73.- 配套讲稿:
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