葡萄膜黑色素瘤生存预后相关lncRNA的初步筛选及相关性分析

目的：:通过构建lncRNA-miRNA-mRNA的内源竞争RNA（ceRNA）网络,筛选与葡萄膜黑色素瘤（UM）生存预后相关的长链非编码RNA（lncRNA）,并进行相关性分析。方法：:以生物信息学为手段,通过疾病预后相关分析,LncRNA亚细胞定位检索,从肿瘤基因组图谱数据库中筛选lncRNA表达数据集。通过mir...     

RNA干扰技术在葡萄膜黑色素瘤治疗中的展望

葡萄膜黑色素瘤是成年人中最多见的一种恶性肿瘤。该肿瘤恶性程度高，预后较差，易行血流转移，主要通过眼球摘除术及相应的放疗、化疗治疗，但效果均不理想和确切。RNA干扰技术的出现已成为生命科学研究和临床治疗的又一次革命。利用RNA干扰技术，体外合成葡萄膜黑色素瘤中的相关的小片段核苷酸（19核苷酸），通过基因工程方法构建质粒，转染人葡萄膜黑色素瘤细胞，对葡萄膜黑色素瘤基因表达产生抑制作用，将会成为治疗葡萄膜黑色素瘤的一条新途径。     

长链非编码RNA在糖尿病视网膜病变发展及治疗中的研究进展

DR是世界各地工作年龄段成年人失明的主要原因，其发病机制是多因素的，分子机制尚不完全清楚。长链非编码RNA（lncRNAs）被认为是多细胞功能的关键调节因子，已有证据表明其参与了DR的许多病理生理机制，本文就 lncRNAs在DR中发挥功能的分子机制及调控作用进行综述，为今后DR的防治研究提供一定的策略和方向。     

葡萄膜恶性黑色素瘤转移相关的非编码RNA表达谱及竞争性内源RNA调控网络分析

目的:利用生物信息学方法分析与葡萄膜恶性黑色素瘤转移相关的非编码RNA,以及它们作为竞争性内源RNA的作用机制.方法:从癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库下载80例葡萄膜恶性黑色素瘤患者的RNA测序数据和临床资料,采用edgeR算法分析转移与非转移患者组织中差异表达(dif...     

长链非编码RNA在眼科疾病中的研究进展

通过全基因组的分析揭示了90％人类基因是被转录的。然而,大约只有1％RNA转录子可以编码蛋白质,其他的是非编码RNA。非编码RNA按照长度可以大致地被区分为小非编码RNA （＜200 nt ）,包括微小RNA、转运RNA、核仁小RNA等;长链RNA （＞200 nt ）包括核糖体RNA,自然反义转录子,和其他的长链非编码RNA等。尽管生物信息学及生物活性分析已经使很多小非编码RNA的功能得到开发,但是我们对于长链非编码RNA（ LncRNA）却知之甚少。 LncRNAs在调节基因转录、转录后翻译,表观遗传学水平扮演多个角色。 LncRNAs异常表达可能发生在各种病理过程中,许多LncRNAs特异表达都与眼科疾病的发生和治疗效果不佳明显相关。在本文中,我们将对眼科常见疾病相关 LncRNAs 的功能特点和调控作用进行综述。     

长链非编码RNA与眼的发育和疾病

长链非编码RNA(long non-coding RNAs,lncRNAs)是长度大于200个核苷酸的非编码RNA,具有数量多、类型多、作用模式多等特点。lncRNAs生物学功能涉及基因印记、染色质重塑、mRNAs的剪切降解及翻译的调控、细胞周期调控和细胞分化调控、免疫监视,构成细胞核亚结构的骨架等,在个体发育和人类疾病中发挥着重要的作用。本文主要对目前已发现的、与眼的发育和疾病密切相关的lncRNAs做一综述。     

非编码RNA与白内障发病关系的研究进展

白内障是我国乃至全世界首要致盲眼病,其发病机制仍未明确,也尚无有效药物治疗方式。非编码 RNA(non-coding RNA,ncRNA)是一类不具备蛋白编码功能的RNA。 已有研究证明ncRNA与人类疾病的发生发展密切相关,其中ncRNA与眼科疾病的研究也日益增多。本文主要就微小RNA、 长链非编码RNA和环状RNA在白内障中的研究进展进行总结,发现对微小RNA与白内障关系的研究较多,而长链非编码RNA和环状RNA在白内障发病机制中的研究近2年才逐渐开展,因此需要眼科医生进一步深入探究,从而为白内障的防治提供新思路与新方法。     

非编码RNA与青光眼的研究进展

青光眼是一种不可逆的、进行性的视神经退行性疾病,是全世界第2位致盲性眼病。近年来研究发现,青光眼的发病机制复杂,非编码RNA在青光眼的发生、发展过程中起重要作用,包括微小RNA、长链非编码RNA以及环状RNA,这些都有望成为青光眼诊断或治疗的新靶点,给青光眼的诊断、治疗提供了新的思路和方法。本文将针对非编码RNA与青光眼相关的研究进展进行综述,以期对临床科研提供参考。     

miRNA在葡萄膜黑色素瘤诊断中的应用

葡萄膜黑色素瘤是成年人最常见的原发性眼内恶性肿瘤,其诊断方法是通过间接检眼镜所见结合彩色超声、磁共振成像等影像学检查,患者就诊时往往已发展到晚期.葡萄膜黑色素瘤的治疗包括激光光凝治疗、放射治疗、肿瘤局部切除和眼球摘除,均未明显提高患者的生存率.微小RNA是一种长约21～25个核苷酸的RNA,参与了包括个体发育、细胞凋亡、细胞增生与分化、肿瘤发生等生命过程.所以miRNA可作为葡萄膜黑色素瘤新的分子标志物,其检测可能对诊断疾病及判断预后提供有价值的依据,为针对目标微小RNA进行基因治疗提供理论依据.     

长链非编码RNA（lncRNA）核仁小RNA宿主基因7（SNHG7）对葡萄膜黑色素瘤癌细胞增殖和侵袭力的影响

目的　探讨长链非编码RNA（lncRNA）核仁小RNA宿主基因7（SNHG7）对葡萄膜黑色素瘤癌细胞增殖和侵袭力的影响。方法　选取2011年8月至2019年8月在我院行手术治疗的葡萄膜黑色素瘤患者71例71眼作为葡萄膜黑色素瘤组,另选取因外伤摘除且葡萄膜完整、眼球正常的患者40例40眼作为正常组。两组患者性别、年龄、患眼眼别差异均无统计学意义（均为P>0.05）。采用实时荧光定量PCR检测两组患者眼球组织中SNHG7表达。取M23细胞进行培养,将对数生长期细胞分成3组,SNHG7干扰组:转染SNHG7干扰序列;阴性对照组:转染阴性对照序列;空白组:不作任何处理。采用实时荧光定量PCR检测各组细胞中SNHG7表达,CCK-8法检测转染后细胞增殖活性,Transwell法检测细胞侵袭力。结果　葡萄膜黑色素瘤组患者眼球组织中SNHG7的相对表达量为2.05±0.16,正常组患者眼球组织中SNHG7的相对表达量为1.01±0.07,两组差异有统计学意义（t=39.461,P<0.001）。葡萄膜黑色素瘤组在发生巩膜浸润和眼外生长的患者眼球组织中SNHG7相对表达量均较无巩膜浸润和无眼外生长的患者高,差异均有统计学意义（均为P<0.05）。转染后继续培养48 h,SNHG7干扰组细胞SNHG7相对表达量（0.27±0.09）明显低于阴性对照组（1.01±0.07）和空白组（1.03±0.09）（均为P<0.001）。与阴性对照组和空白组相比,SNHG7干扰组细胞转染后24 h、48 h、72 h和96 h时光密度均降低,差异均有统计学意义（均为P<0.05）。转染后48 h,SNHG7干扰组侵袭细胞数［（89.77±9.82）个］显著低于阴性对照组［（133.14±7.54）个］和空白组［（137.09±10.05）个］（均为P<0.001）。结论　葡萄膜黑色素瘤患者眼球组织中SNHG7呈高表达,且SNHG7高表达与肿瘤组织巩膜浸润和眼外生长有关,下调SNHG7基因表达可阻碍M23细胞增殖和侵袭。     

MicroRNA在葡萄膜恶性黑色素瘤中的研究进展

恶性黑色素瘤恶性程度高,易经血流转移,是成年人中最多见的一种恶性眼内肿瘤,其发生发展涉及到多步骤的分子生物学机制,包括原癌基因和抑癌基因的遗传和表观遗传学改变。因此研究参与此过程的分子机制能为肿瘤的有效治疗提供有益的见解。微小核糖核酸（ｍｉｃｒｏＲＮＡ,ｍｉＲＮＡ）是一类长约２２个核苷酸的非编码单链小分子ＲＮＡ,在各种生理病理过程中发挥了重要作用,最新的研究发现,异常表达的ｍｉｃｒｏＲＮＡ参与了葡萄膜恶性黑色素瘤众多的病理过程。本文综述了ｍｉｃｒｏＲＮＡ的发现、形成及作用机制,葡萄膜恶性黑色素瘤中ｍｉｃｒｏＲＮＡ的异常表达及其可能机制,ｍｉｃｒｏＲＮＡ与葡萄膜恶性黑色素瘤的发生与增殖、侵袭和转移以及ｍｉｃｒｏＲＮＡ在葡萄膜恶性黑色素瘤中的临床应用价值。     

Iris melanoma in a patient with neurofibromatosis

Neurofibromatosis type 1 (NF1) is a common autosomal dominant hamartomatous disorder, which is considered to be a neurocristopathy. Uveal melanoma, also of neural crest origin, is the most common primary malignant intraocular tumor in adults. The association of NF1 and uveal melanoma is controversial. We present a clinicopathologic report of iris melanoma in a patient with NF1 and review the literature for a possible causal association. To our knowledge, only 18 cases of uveal melanoma, including three cases of iris melanoma, have been reported in association with NF1. On the basis of the prevalence of NF1 (1 in 3000) and the prevalence of uveal melanoma (1 in 13,500), it can be estimated that approximately seven patients with NF1 in the United States would have an associated uveal melanoma by chance alone. We conclude that despite the theoretical possibility of a causal association of uveal melanoma and NF1, it may still be regarded as coincidental in the absence of any strong evidence to the contrary.     

Iris melanoma arising in iris nevus in oculo(dermal) melanocytosis

A 50-year-old white man with oculo(dermal) melanocytosis and longstanding iris nevus was found to have growth of the iris mass. Excision and histopathologic examination revealed a mixed cell type malignant melanoma. Benign nevus cells were present at the periphery of the tumor surrounding the entire melanoma. White patients with oculo(dermal) melanocytosis have a predisposition to uveal melanoma, which is usually choroidal in origin. Literature review showed only three confirmed cases of iris melanoma in this setting. Two additional cases initially published as spindle A melanoma have been reclassified as iris nevi based on the modified Callender classification of uveal melanomas. It is recommended that patients with oculo(dermal) melanocytosis be followed for the occurrence of uveal melanoma.     

长链非编码RNA在眼部疾病的研究进展

长链非编码RNA(lncRNA)被定义为长度超过200个核苷酸并从人类基因组转录而未翻译(非编码)的RNA。随着人类基因组测序及图谱绘制的顺利完成,在随后启动的ENCODE研究中发现,约75%的基因组序列可以被转录成RNA,而其中大部分转录产物为非编码RNA。近年研究发现,lncRNA广泛参与生物个体的发育、细胞增殖、细胞分化等体内多种重要的生理及病理过程,如细胞周期调控、细胞代谢、细胞凋亡、诱导多能干细胞的重编程及表观遗传调控等生物学功能,而差异性表达对人类各种疾病的发生起着重要的作用,如恶性肿瘤、炎症及免疫性疾病等。研究表明lncRNA与眼科疾病的发病机制也密切相关,本文对近年来关于lncRNA的异常表达与眼部疾病的研究现状做一综述。     

Molecular regulation of vasculogenic mimicry in human uveal melanoma cells: role of helix–loop–helix Id2 (inhibitor of DNA binding 2)

Background  Vasculogenic mimicry (VM) is a tumor angiogenesis process in which highly aggressive melanoma cells form patterned, tubular networks in an in vitro, three-dimensional culture that mimics vasculogenic networks formed by endothelial cells. These cells also express endothelial cell-associated genes such as vascular endothelial–cadherin (VE–cadherin) and are correlated with poor clinical prognosis in patients. However, the molecular underpinnings of this phenomenon remain elusive. Methods  Three-dimensional cultures of highly and poorly aggressive uveal melanoma cells were observed by inverted light microscope and scanning electronic microscope for VM. RNAi (RNA interference) technology was used to examine whether inhibitor of DNA binding 2 (Id2) was involved in the uveal melanoma vasculogenic mimicry. Western blot analysis showed changes of Id2 and VE-cadherin expression in highly and poorly aggressive melanoma cells in vitro. Migration analysis of highly and poorly aggressive uveal melanoma cells in vitro illuminated the role of Id2 in tumor cells migration. Results  We show here that a transient knockdown of Id2 by RNA interference abrogates VM and VE-cadherin expression in highly aggressive uveal melanoma cells. Furthermore, inhibition of Id2 changes cellular stability and creates a more dynamic condition. Transfected cells also migrate better than untransfected cells. Conclusions  This study shows that Id2 is an important regulator of VM. Specifically, Id2 affects VE-cadherin expression, and is critical for the formation of vasculogenic-like networks. Grant  Beijing Municipal Natural Science Foundation (7053065).     

Telomerase expression in uveal melanoma

BACKGROUND/AIMS: Accumulating evidence indicates that telomerase activity is repressed in normal human somatic cells but reactivated in cancers and immortal cells, suggesting that activation of telomerase activity has a role in carcinogenesis and immortalisation. To date, telomerase in uveal melanoma and, whether, it may have a role in the development or progression of these tumours has not been described. The expression patterns and the activity of telomerase were investigated in 14 uveal melanoma and these results were correlated with histological and immunohistological features of these tumours. METHODS: A modified PCR based telomeric repeat amplification protocol (TRAP) assay was used to demonstrate telomerase activity in 14 uveal melanomas. In addition, in situ hybridisation was used to demonstrate the expression pattern of the telomerase RNA component (hTR) at the single cell level in eight of these globes. RESULTS: The TRAP assay revealed moderate telomerase activity in all uveal melanomas examined. In situ hybridisation visualised a moderate to high upregulation of hTR in the melanoma cells but not in the admixed reactive cells. There was no correlation among tumour location, cell type, or growth fraction and the amount of telomerase activity. In addition, the cells of the germinative zone of the lens demonstrated a strong hTR expression. CONCLUSION: Telomerase activity is upregulated in uveal melanomas. The expression of hTR was located to the tumour cells and not the reactive tumour infiltrating cells. Strong telomerase expression was also demonstrated in cells of the germinative zone of the lens.