miRNA与大肠癌关系的研究进展

微小RNA（miRNA）是一类进化上保守内源性非蛋白质编码的RNA分子,长约17～25个核苷酸,能够识别特定的目标mRNA,并有在转录后水平负调控基因的表现。结肠肿瘤组织和血液中的miRNA可以准确地诊断大肠癌和帮助预测疾病复发。特异miRNA的过度表达和沉默与大肠癌的进展有关。miRNA在肿瘤形成中的作用表明其可能是重要的基因治疗目标。组织和血液中特异miRNA的表达不同,提示了其在大肠癌早期发现和筛检中的应用前景。miRNA还能预测转移和耐药性。     

外周血miRNA作为肿瘤标志物的研究进展

miRNA是一类长度为20～24个核苷酸的非编码小分子RNA,与靶基因3'端非编码区不完全配对,从而抑制靶基因mRNA的翻译,影响个体发育、细胞凋亡、细胞增殖和分化等生命活动,与肿瘤的发生、转移和耐药等病理进程密切相关.近年来的研究发现,除了组织和细胞中的miRNA,外周血miRNA的表达也表现为显著的肿瘤相关性、组织特异性和表达稳定性,符合肿瘤标志物的要求.本文就外周血miRNA作为肿瘤标志物的研究进展进行综述.     

微RNA与肿瘤

微RNA(miRNA)是一类非编码的小RNA分子,通过直接抑制基因转录或蛋白质的表达而在器官发育,细胞增殖、分化和凋亡等多种生理过程中发挥关键作用.miRNA异常表达往往导致包括肿瘤在内的多种疾病.研究发现,miRNA在肿瘤发生发展、侵袭转移及肿瘤的诊治中起着重要作用.     

微RNA与肿瘤

微RNA（miRNA）是一类非编码的小RNA分子,通过直接抑制基因转录或蛋白质的表达而在器官发育,细胞增殖、分化和凋亡等多种生理过程中发挥关键作用.miRNA异常表达往往导致包括肿瘤在内的多种疾病.研究发现,miRNA在肿瘤发生发展、侵袭转移及肿瘤的诊治中起着重要作用.     

微RNA与肿瘤

微RNA(miRNA)是一类非编码的小RNA分子,通过直接抑制基因转录或蛋白质的表达而在器官发育,细胞增殖、分化和凋亡等多种生理过程中发挥关键作用.miRNA异常表达往往导致包括肿瘤在内的多种疾病.研究发现,miRNA在肿瘤发生发展、侵袭转移及肿瘤的诊治中起着重要作用.     

微小RNA与肿瘤

近年来微小RNA(miRNA)逐渐成为肿瘤研究的热点.越来越多的研究表明,miRNA已涉及到肿瘤的发生和发展,miRNA的表达与肿瘤的病理进程具有相关性,大约有数百个miRNA在肿瘤中异常表达,miRNA在不同肿瘤中具有时空特异性的表达谱.     

微小RNA与肿瘤的关系

微小RNA（microRNA,miRNA）是一类长度约为22个核苷酸的内源性单链非编码小RNA分子,通过碱基配对原则与靶基因完全或不完全互补结合,调控基因表达,调节细胞分化、细胞增殖、血管生成和细胞凋亡等过程。miRNA异常表达,可作为癌基因或抑癌基因介导恶性肿瘤的发生发展、复发和转移等。miRNA的表达具有组织特异性,使其能够在不明组织来源肿瘤中起诊断作用。通过不同的药物输送途径上调或抑制miRNA的表达,靶向调节miRNA成为一种新的治疗手段,开启了肿瘤治疗新模式。     

80例结肠癌患者血浆、组织中microRNA 100/200c表达水平与临床病理的相关性

摘 要：［目的］ 研究结肠癌患者血浆、组织中小分子非编码RNA (microRNA,miRNA) 100/200c表达水平与临床病理的相关性。［方法］ 用实时定量PCR方法测定确诊为结肠癌的80例患者血浆miRNA 100、结肠癌组织中miRNA 200c表达水平并与其在正常人群血浆及癌旁正常组织中的表达进行比较。［结果］ 结肠癌患者血浆中miRNA 100的表达水平显著性低于正常人群（P=0.014）,结肠癌组织中miRNA 200c表达量显著性低于癌旁正常组织（P=0.0002）;结肠癌患者血浆中miRNA 100相对表达量与肿瘤分化程度、发生转移、临床分期显著性相关（P＜0.05）,且miRNA 100表达高低与患者的肿瘤直径,临床分期、淋巴结转移相关（P<0.05）;结肠癌组织中miRNA 200c表达量与发生转移、临床分期显著性相关（P＜0.05）,miRNA2000表达高低与肿瘤直径大小相关（P＜0.05）。［结论］ 与在正常组织或血浆中相比,miRNA 100/200c在结肠癌中表达量降低,与肿瘤远处转移、淋巴结转移、临床分期等病理参数密切相关。     

微小RNA与肿瘤研究进展

微小RNA(microRNA,miRNA)是一种长度约为22 nt的非编码RNA,它们通过miRNA介导的特异性的基因沉默导致靶mRNA降解及抑制蛋白质的合成调控转录后基因表达水平.miRNA对细胞的增殖、分化和凋亡有重要的调节作用,在正常组织和肿瘤组织中的表达显著不同,参与了肿瘤的发生、发展和预后.该文主要讨论miRNA在肿瘤方面的研究进展.     

Drosha 蛋白在乳腺癌中的表达及其临床意义

乳腺癌是一个基因组疾病,是一个多因素参与、多步骤的发生发展过程。微小 RNA（microRNA）是一类普遍存在于多种细胞生物中、长度为18～22个核苷酸的的内源性非编码小RNA 分子,它通过与信使 RNA3末端结合沉默或降解基因,最终抑制蛋白质翻译。作为重要的调控分子之一,miRNA 可直接或间接影响细胞的时序发育、增殖、凋亡、黏附、血管形成、迁移、转移等过程。近年来越来越多的研究表明,miRNA 的异常表达与肿瘤的发生、发展等过程密切相关。Drosha 蛋白是miRNA 成熟过程中起首关切割作用的核酸内切酶之一,Dro-sha 蛋白的异常表达可以导致 miRNA 的整体异常表达,从而导致肿瘤的发生发展。最近研究证实,在肺癌、卵巢癌等多种肿瘤中存在 Drosha 的表达下调,并证实 Drosha 表达水平与患者预后相关。miRNA 和 RNA 干扰途径中的关键酶 Drosha 的表达量改变与肿瘤的发生密切相关,但其在不同肿瘤中的研究结果并不一致［1-5］。     

核心蛋白聚糖基因在肿瘤学中的研究进展

核心蛋白聚糖( Decorin,DCN)是富含亮氨酸小分子蛋白多糖家族成员之一,是公认的抑癌基因,可结合并灭活转化生长因子β( TGF-β)和抑制血管内皮生长因子( VEGF)表达,还可通过激活EG-FR/MAP激酶/p21信号通路介导的促细胞增殖信号通路等机制来抑制肿瘤细胞增殖与转移,在肿瘤的发展、血管形成、转移过程中具有重要作用. DCN在多种恶性肿瘤中表达,通过上调或下调DCN的表达,能够使DCN通过多种途径发挥其抗肿瘤活性,降低、延缓多种恶性肿瘤的发生、发展. DCN基因可能成为多种恶性肿瘤治疗的潜在靶点.     

TGF-² Signaling Pathway in Lung Adenocarcinoma Invasion

The histologic distinction between bronchioloalveolar carcinoma and other adenocarcinomas is tissue invasion. The clinical importance of lung adenocarcinoma invasion is supported by several recent studies indicating that the risk of death in nonmucinous bronchioloalveolar carcinoma is significantly lower than that of pure invasive tumors and in tumors with greater than 0.5 cm of fibrosis or linear invasion. Using microarray gene expression profiling of human tumors, dysregulation of transforming growth factor-² signaling was identified as an important mediator of tumor invasion. Subsequent studies showed that the CC chemokine regulated on activation, normal T cell expressed, and presumably secreted was up-regulated in invasive tumors and was required for invasion in cells with repressed levels of the transforming growth factor-² type II receptor. Taken together, these studies illustrate how information gained from global expression profiling of tumors can be used to identify key pathways and genes mediating tumor growth, invasion, and metastasis.     

Metastasis signatures: genes regulating tumor–microenvironment interactions predict metastatic behavior

The possibility of predicting clinical outcome of cancer patients through the analysis of gene expression profiles in the primary tumor is a kind of ideological revolution as the multistep carcinogenesis model postulates that the proportion of cells within the primary tumor that actually acquire metastasis driving mutation(s) is small; too small to leave its imprint on the gene expression profile. The data collected to date have brought a new paradigm to reality in the metastasis field: metastasis must at least in part rely on mutations and/or gene regulation events present in the majority of cells which constitute the primary tumor mass. By analyses of differential expression of primary tumors versus metastases or by functional analyses of putative metastasis genes in experimental metastasis, many metastasis-associated gene expression events have been identified that correlate with the development of metastases. Among genes “favoring” metastasis, we find many molecules that are expressed not by the tumor cell itself but by the cells of the microenvironment, as well as genes over-expressed in the primary tumor that have a principle role in mediating tumor–host interactions. Here we review these concepts and advance hypotheses on how gene expression of the primary tumor and the microenvironment can favor the spread of the metastasis seeds and how this knowledge can provide tools to secondary prevention.     

微小RNA miR-155在肿瘤中的研究

微小RNA miR-155在多种人体肿瘤中异常表达,与肿瘤的发生、发展及预后密切相关,被认为是癌性微小RNA(oncomiR).研究发现miR-155可通过抑制其靶基因如SHIP1、C/EBPβ、SOCS1、TP53INP1等促进肿瘤的增殖、侵袭及转移.检测miR-155的表达可对早期诊断恶性肿瘤提供重要依据,抑制其表达将成为肿瘤治疗的新方向.     

CD44v9基因在恶性卵巢肿瘤中的表达及其临床意义

目的：探讨恶性缲ＣＤ４４Ｖ８基因表达及其临床意义。方法：用ＲＴ－ＰＣＲ方法检测了４１例恶性卵巢肿瘤、２０例良性卵巢肿瘤和２１例正常卵巢组织中ＣＤ４４Ｖ９基因表达情况并分析相关的临床病理因素。结果：１）ＣＤ４４Ｖ９基因表达阳性纺恶性组明显高于良性组和正常组，良性组高于正常组：２）ＣＤ４４Ｖ９基因表达在有转移者阳性率显著高于无转移者，转移灶阳性率高于原发灶：３）ＣＤ４４Ｖ９阳性表达率与临床期别有一定关     

SPARCL1基因在肿瘤中的表达及作用

富含半胱氨酸的酸性分泌蛋白类似蛋白1（SPARCL1）基因的异常表达与多种肿瘤的发展、转移及预后密切相关。近年来研究表明，SPARCL1基因在脑胶质瘤中表达升高，其编码的蛋白可以和胶原相互作用，从而影响肿瘤的转移能力，与肿瘤恶性程度呈正相关。SPARCL1基因在胃癌、结直肠癌、前列腺癌及乳腺癌等肿瘤组织中低表达，与肿瘤的侵袭及转移能力呈负相关。目前对于 SPARCL1基因发挥作用的具体分子机制仍存在争议，其在肿瘤组织中的表达和功能似乎依赖于肿瘤微环境。     

Thymidylate synthase and dihydropyrimidine dehydrogenase gene expressions in colorectal cancer using the Danenberg tumor profile method

Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) have been identified as a predictor of response to 5-fluorouracil (5-FU). Danenberg et al. developed a technology to evaluate gene expressions in formalin-fixed paraffin-embedded (FFPE) specimens (DTP; Danenberg tumor profile). In this study, TS and DPD gene expressions were measured in 47 primary colorectal cancer tumors and 12 metastatic tumors using FFPE specimens. In primary tumors, expression of TS genes in cancerous tissues was statistically higher than in stromal tissues, while DPD gene expressions in stromal tissues were higher than those in cancerous tissues. The median TS mRNA level was 0.86 in hepatic metastasis and 1.95 in lymph node metastasis. The median DPD mRNA level was 0.86 in hepatic metastasis and 1.96 in lymph node metastasis. Both gene expressions differed among primary tumors and metastatic tumors, especially in metastatic sites. DTP might be useful to evaluate the 2 gene expressions in colorectal cancer. Further studies would be needed to clarify the mechanisms of difference of gene expressions in cancerous and stromal tissues, or in primary tumors and metastatic tumors.     

Distinct hypermethylation profile of primary breast cancer is associated with sentinel lymph node metastasis.

PURPOSE: Gene promoter region hypermethylation is a significant event in primary breast cancer. However, its impact on tumor progression and potential predictive implications remain relatively unknown. EXPERIMENTAL DESIGN: We conducted hypermethylation profiling of 151 primary breast tumors with association to known prognostic factors in breast cancer using methylation-specific PCR for six known tumor suppressor and related genes: RASSF1A, APC, TWIST, CDH1, GSTP1, and RAR-beta2. Furthermore, correlation with sentinel lymph node (SLN) tumor status was assessed as it represents the earliest stage of metastasis that is readily detected. Hypermethylation for any one gene was identified in 147 (97%) of 151 primary breast tumors. The most frequently hypermethylated gene was RASSF1A (81%). RESULTS: Hypermethylation of the CDH1 was significantly associated with primary breast tumors demonstrating lymphovascular invasion (P = 0.008), infiltrating ductal histology (P = 0.03), and negative for the estrogen receptor (P = 0.005), whereas RASSF1A and RAR-beta2 gene hypermethylation were significantly more common in estrogen receptor-positive (P < 0.001) and human epidermal growth factor receptor 2-positive (P < 0.001) tumors, respectively. In multivariate analysis, hypermethylation of GSTP1 and/or RAR-beta2 was significantly associated with patients having macroscopic SLN metastasis compared with those with microscopic or no sentinel node metastasis (odds ratio, 4.59; 95% confidence interval, 2.02-10.4; P < 0.001). In paired SLN metastasis, CDH1 was the most frequently methylated gene (90%) and provides evidence in patients corroborating its role in the clinical development of metastasis. CONCLUSION: Hypermethylation profiling of primary breast tumors is significantly associated with known pathologic prognostic factors and may have additional clinical and pathologic utility for assessing patient prognosis and predicting early regional metastasis.