microRNA与黑素瘤

microRNA是一种大小约22个核苷酸的非编码单链小RNA分子,参与细胞增殖、分化、凋亡等多种重要细胞活动的调控.近来研究发现,microRNA具有癌基因或抑癌基因样作用,在人类恶性肿瘤的发生、发展中起重要作用.目前已发现数种microRNA在黑素瘤细胞表达异常,其中microRNA-221和microRNA-222在黑素瘤中表达升高,可以通过下调p27Kip1/CDKN1B和c-KIT受体两条通路来促进黑素细胞的恶性转化,在黑素瘤中发挥癌基因样作用.而microRNA-137、-34a、-199a和let-7家族成员let-7a、let-7b等,分别下调相应的靶基因,在黑素瘤中发挥抑癌基因样的作用.microRNA对黑素瘤相关基因的表达调控研究,不仅探讨早期黑素瘤发生的新的调节机制,而且为将来靶向治疗开辟道路.     

microRNA与黑素瘤

microRNA是一种大小约22个核苷酸的非编码单链小RNA分子,参与细胞增殖、分化、凋亡等多种重要细胞活动的调控.近来研究发现,microRNA具有癌基因或抑癌基因样作用,在人类恶性肿瘤的发生、发展中起重要作用.目前已发现数种microRNA在黑素瘤细胞表达异常,其中microRNA-221和microRNA-222在黑素瘤中表达升高,可以通过下调p27Kip1/CDKN1B和c-KIT受体两条通路来促进黑素细胞的恶性转化,在黑素瘤中发挥癌基因样作用.而microRNA-137、-34a、-199a和let-7家族成员let-7a、let-7b等,分别下调相应的靶基因,在黑素瘤中发挥抑癌基因样的作用.microRNA对黑素瘤相关基因的表达调控研究,不仅探讨早期黑素瘤发生的新的调节机制,而且为将来靶向治疗开辟道路.     

microRNA与黑素瘤

microRNA是一种大小约22个核苷酸的非编码单链小RNA分子,参与细胞增殖、分化、凋亡等多种重要细胞活动的调控.近来研究发现,microRNA具有癌基因或抑癌基因样作用,在人类恶性肿瘤的发生、发展中起重要作用.目前已发现数种microRNA在黑素瘤细胞表达异常,其中microRNA-221和microRNA-222在黑素瘤中表达升高,可以通过下调p27Kip1/CDKN1B和c-KIT受体两条通路来促进黑素细胞的恶性转化,在黑素瘤中发挥癌基因样作用.而microRNA-137、-34a、-199a和let-7家族成员let-7a、let-7b等,分别下调相应的靶基因,在黑素瘤中发挥抑癌基因样的作用.microRNA对黑素瘤相关基因的表达调控研究,不仅探讨早期黑素瘤发生的新的调节机制,而且为将来靶向治疗开辟道路.     

microRNA与黑素瘤

microRNA是一种大小约22个核苷酸的非编码单链小RNA分子,参与细胞增殖、分化、凋亡等多种重要细胞活动的调控.近来研究发现,microRNA具有癌基因或抑癌基因样作用,在人类恶性肿瘤的发生、发展中起重要作用.目前已发现数种microRNA在黑素瘤细胞表达异常,其中microRNA-221和microRNA-222在黑素瘤中表达升高,可以通过下调p27Kip1/CDKN1B和c-KIT受体两条通路来促进黑素细胞的恶性转化,在黑素瘤中发挥癌基因样作用.而microRNA-137、-34a、-199a和let-7家族成员let-7a、let-7b等,分别下调相应的靶基因,在黑素瘤中发挥抑癌基因样的作用.microRNA对黑素瘤相关基因的表达调控研究,不仅探讨早期黑素瘤发生的新的调节机制,而且为将来靶向治疗开辟道路.     

microRNA与黑素瘤

microRNA是一种大小约22个核苷酸的非编码单链小RNA分子,参与细胞增殖、分化、凋亡等多种重要细胞活动的调控.近来研究发现,microRNA具有癌基因或抑癌基因样作用,在人类恶性肿瘤的发生、发展中起重要作用.目前已发现数种microRNA在黑素瘤细胞表达异常,其中microRNA-221和microRNA-222在黑素瘤中表达升高,可以通过下调p27Kip1/CDKN1B和c-KIT受体两条通路来促进黑素细胞的恶性转化,在黑素瘤中发挥癌基因样作用.而microRNA-137、-34a、-199a和let-7家族成员let-7a、let-7b等,分别下调相应的靶基因,在黑素瘤中发挥抑癌基因样的作用.microRNA对黑素瘤相关基因的表达调控研究,不仅探讨早期黑素瘤发生的新的调节机制,而且为将来靶向治疗开辟道路.     

microRNA与黑素瘤

microRNA是一种大小约22个核苷酸的非编码单链小RNA分子,参与细胞增殖、分化、凋亡等多种重要细胞活动的调控.近来研究发现,microRNA具有癌基因或抑癌基因样作用,在人类恶性肿瘤的发生、发展中起重要作用.目前已发现数种microRNA在黑素瘤细胞表达异常,其中microRNA-221和microRNA-222在黑素瘤中表达升高,可以通过下调p27Kip1/CDKN1B和c-KIT受体两条通路来促进黑素细胞的恶性转化,在黑素瘤中发挥癌基因样作用.而microRNA-137、-34a、-199a和let-7家族成员let-7a、let-7b等,分别下调相应的靶基因,在黑素瘤中发挥抑癌基因样的作用.microRNA对黑素瘤相关基因的表达调控研究,不仅探讨早期黑素瘤发生的新的调节机制,而且为将来靶向治疗开辟道路.     

microRNA与黑素瘤

microRNA是一种大小约22个核苷酸的非编码单链小RNA分子,参与细胞增殖、分化、凋亡等多种重要细胞活动的调控.近来研究发现,microRNA具有癌基因或抑癌基因样作用,在人类恶性肿瘤的发生、发展中起重要作用.目前已发现数种microRNA在黑素瘤细胞表达异常,其中microRNA-221和microRNA-222在黑素瘤中表达升高,可以通过下调p27Kip1/CDKN1B和c-KIT受体两条通路来促进黑素细胞的恶性转化,在黑素瘤中发挥癌基因样作用.而microRNA-137、-34a、-199a和let-7家族成员let-7a、let-7b等,分别下调相应的靶基因,在黑素瘤中发挥抑癌基因样的作用.microRNA对黑素瘤相关基因的表达调控研究,不仅探讨早期黑素瘤发生的新的调节机制,而且为将来靶向治疗开辟道路.     

microRNA与黑素瘤

microRNA是一种大小约22个核苷酸的非编码单链小RNA分子,参与细胞增殖、分化、凋亡等多种重要细胞活动的调控.近来研究发现,microRNA具有癌基因或抑癌基因样作用,在人类恶性肿瘤的发生、发展中起重要作用.目前已发现数种microRNA在黑素瘤细胞表达异常,其中microRNA-221和microRNA-222在黑素瘤中表达升高,可以通过下调p27Kip1/CDKN1B和c-KIT受体两条通路来促进黑素细胞的恶性转化,在黑素瘤中发挥癌基因样作用.而microRNA-137、-34a、-199a和let-7家族成员let-7a、let-7b等,分别下调相应的靶基因,在黑素瘤中发挥抑癌基因样的作用.microRNA对黑素瘤相关基因的表达调控研究,不仅探讨早期黑素瘤发生的新的调节机制,而且为将来靶向治疗开辟道路.     

microRNA与黑素瘤

microRNA是一种大小约22个核苷酸的非编码单链小RNA分子,参与细胞增殖、分化、凋亡等多种重要细胞活动的调控.近来研究发现,microRNA具有癌基因或抑癌基因样作用,在人类恶性肿瘤的发生、发展中起重要作用.目前已发现数种microRNA在黑素瘤细胞表达异常,其中microRNA-221和microRNA-222在黑素瘤中表达升高,可以通过下调p27Kip1/CDKN1B和c-KIT受体两条通路来促进黑素细胞的恶性转化,在黑素瘤中发挥癌基因样作用.而microRNA-137、-34a、-199a和let-7家族成员let-7a、let-7b等,分别下调相应的靶基因,在黑素瘤中发挥抑癌基因样的作用.microRNA对黑素瘤相关基因的表达调控研究,不仅探讨早期黑素瘤发生的新的调节机制,而且为将来靶向治疗开辟道路.     

microRNA与黑素瘤

microRNA是一种大小约22个核苷酸的非编码单链小RNA分子,参与细胞增殖、分化、凋亡等多种重要细胞活动的调控.近来研究发现,microRNA具有癌基因或抑癌基因样作用,在人类恶性肿瘤的发生、发展中起重要作用.目前已发现数种microRNA在黑素瘤细胞表达异常,其中microRNA-221和microRNA-222在黑素瘤中表达升高,可以通过下调p27Kip1/CDKN1B和c-KIT受体两条通路来促进黑素细胞的恶性转化,在黑素瘤中发挥癌基因样作用.而microRNA-137、-34a、-199a和let-7家族成员let-7a、let-7b等,分别下调相应的靶基因,在黑素瘤中发挥抑癌基因样的作用.microRNA对黑素瘤相关基因的表达调控研究,不仅探讨早期黑素瘤发生的新的调节机制,而且为将来靶向治疗开辟道路.     

Distinction of desmoplastic melanoma from non-desmoplastic melanoma by gene expression profiling

Desmoplastic melanoma (DM) is a variant of melanoma characterized by the presence of amelanotic fusiform melanocytes dispersed in a prominent collagenous stroma. DM behaves differently from conventional non-desmoplastic melanoma (NDM). It has a higher tendency for local recurrence and is less likely to metastasize to regional lymph nodes. In this study, we explored the possibility of distinguishing DM from NDM by gene expression profiling. RNA samples from ten primary cutaneous melanomas of similar depth of invasion were analyzed using the Affymetrix U133A oligonucleotide platform. Four tumors were DM, five were ND, and one tumor showed combined features of desmoplastic and conventional. Hierarchical cluster analysis clearly separated DM from NDM. The expression of a number of melanocyte differentiation genes was decreased in DM compared with NDM, which corresponded to immunohistochemical results. Various genes were upregulated in DM, including neurotrophic factors and genes involved in extracellular matrix production. A novel finding was the high expression of clusterin in DM, which was confirmed by immunohistochemical studies. Our results from gene expression profiling validate the distinction of DM from NDM. They also provide the opportunity to learn more about the biology of DM which had previously not yet been associated with this variant of melanoma.     

合并肺间质病变或恶性肿瘤皮肌炎患者的外周血差异基因表达分析

【摘要】 目的 研究合并肺间质病变或恶性肿瘤的皮肌炎/临床无肌病性皮肌炎（DM/CADM）患者的差异表达基因及相关信号通路。方法 2017年1月至2018年1月于上海交通大学医学院附属瑞金医院皮肤科确诊的DM/CADM患者27例，按照合并症状分为3组，即合并肺间质病变组10例，合并恶性肿瘤组8例，无肺间质病变和恶性肿瘤组9例。同时收集7例健康对照。采用高通量RNA测序技术筛选上述4组受试者外周血中差异表达基因，进行基因本体论（GO）分析以及京都基因与基因组百科全书（KEGG）通路富集分析。结果 与健康对照相比，DM/CADM患者4 820条基因表达上调，137条基因表达下调；GO分析获得显著富集条目49个，其中37个（75.5%）与生物过程相关；KEGG分析差异基因富集于感染、肿瘤以及免疫相关通路。与无肺间质病变和恶性肿瘤组相比，合并肺间质病变组272条基因表达上调，158条基因下调；GO分析获得显著富集条目157个，其中114个（72.6%）与生物过程相关；KEGG分析差异基因富集于细菌感染和自身免疫/炎症通路。合并恶性肿瘤组398条基因表达上调，68条基因表达下调；GO分析获得显著富集条目117个，其中94个（80.3%）与生物过程相关；KEGG分析差异基因富集于糖基化、代谢以及肿瘤相关信号通路。结论 DM/CADM患者与健康对照组间、合并肺间质病变或恶性肿瘤的DM/CADM组与无合并症患者组间转录组基因及通路存在差异，细菌感染、细胞因子/趋化因子通路在合并ILD的DM/CADM患者中显著富集，而糖基化、蛋白代谢以及抗原提呈和自然杀伤细胞的细胞毒作用在合并恶性肿瘤的DM/CADM患者中显著富集。     

Retroviruses in dermatology

Retroviruses have a genomic RNA and can induce malignant tumors. Study of the retroviruses led to the discovery of retroviral oncogenes, which were found to be responsible for the development of malignancies. Later on, cellular genes were detected that are closely related to the viral oncogenes but not oncogenic per se. There is strong evidence that retroviruses are associated with cutaneous lymphomas (HTLV I) and AIDS (LAV/HTLV III).     

银屑病差异表达microRNA与靶基因及基因功能调控网络的研究

目的研究银屑病特异表达microRNA(miRNA)与靶基因及基因功能之间调控网络及作用机制。方法采用基因芯片技术筛选银屑病皮损组织和健康皮肤组织中差异性表达的miRNA,并通过生物信息学对差异表达的miRNA进行靶基因预测及靶基因功能富集分析,构建银屑病差异表达miRNA与靶基因及基因功能调控网络,得到网络核心调控的miRNA和受调控作用的核心靶基因及关键性基因功能。结果得出银屑病皮损组织中明显上调的关键miRNA 10个,调控的关键基因12个,主要功能21项,明显下调的关键miRNA 21个,调控的关键基因22个,主要功能28项结论特异性表达的miRNA主要调控的靶基因及其基因功能与银屑病发病密切相关,为银屑病基因层面的机制研究提供了有效的依据。     

A rare case of Sweet syndrome secondary to melioidosis

Background

The tumor microenvironment is composed of cancer-associated fibroblasts, tumor-associated macrophages, endothelial cells, immune cells, signaling molecules and extracellular matrix structures, which closelycommunicate with the tumor via multiple mechanisms. MicroRNAs are paracrine regulators that provide a direct interaction between the microenvironment and cancer cells. In the presentstudy, we aimed to identify the microRNA expression profile in melanoma compared with thatin healthy adjacent skin, with a further assessment of altered microRNA signaling pathways and target genes.

Methods

Formalin-fixed paraffin-embedded (FFPE) melanoma tissue samples were separated by dissection into tumor and surrounding health tissue fragments. MicroRNA expression profiles were obtained by microarray using Gene Atlas Microarray System (Affymetrix, California, USA). To confirm microarray results real-time PCR was carried out. Bioinformatic analysis was performed using the DIANA-miRPath v.3.0 database. Target genes for miR-146a-5p were determined using three algorithms: TargetScan 7.0, miRWalk 2.0 and miRTarBase v.4.5.

Results

A microarray profiling revealed 143 microRNAs asdifferent in tumor versus adjacent tissues. Expression level of hsa-miR-146a-5p showedto be higher in melanoma cells as compared to thehealthy adjacent skin. The bioinformatic study has determined several signaling cascades associated with miR-146a-5p:Toll-like receptor pathway, NF-κB pathway, ErB pathway, and measles signaling pathway. The 38 target genes have been shown for miR-146a-5p of which NRAS gene is known asone of the most frequent mutated in melanoma.

Conclusions

Elucidation of the role of miR-146-a-5p in complex interactions between the tumor and the cells of healthy adjacent skin is necessary for our understanding of the mechanisms oftumor progression. Significant differences found between cancer cells and adjacent tissues in microRNA expression profile corresponding to divergent mRNA/protein levels in these structures should be taken into account when tumor samples characterization estimatedby high-throughput methods.

     

特应性皮炎患儿血清中microRNAs芯片的生物信息学分析

目的：利用生物信息学方法分析特应性皮炎(AD)患儿血清中表达差异的microRNAs (miRNAs),探讨其靶基因的功能及调控的信号通路在疾病的发生发展中的作用。方法：从基因表达综合数据库（GEO）中下载8例AD患儿的血清和8名健康儿童的血清样本中miRNAs的表达数据,利用R 3.4.1软件包筛选差异表达的miRNA,选取其中最具差异表达的miRNA进行后续分析并利用荧光定量PCR进行验证。利用mirTarbase数据库预测其靶基因,采用cytoscape 3.5.1软件及其插件ClueGO、CluePedia进行靶基因的GO功能、KEGG信号通路富集。结果：在AD患儿血清中共筛选出相对于正常对照的差异表达miRNAs 7个,其中上调miRNAs 2个、下调miRNAs 5个。结合文献选取其中最具差异表达的miRNA-126进行下一步分析。荧光定量PCR结果显示,较于健康儿童,AD患儿血清中miRNA-126表达水平下调。数据库共预测出靶基因110个,GO分析显示差异表达基因主要涉及血管通透性的调节、RAC蛋白信号转导、内皮细胞增殖的调节、基质黏附依赖性细胞扩散、活化MAPKK活性、磷蛋白结合等功能,KEGG 分析提示其在包括FoxO信号通路、NF-κB信号通路、B细胞受体信号通路、VEGF信号通路等17个通路中富集。结论：利用生物信息学方法能有效对AD患儿血清中miRNAs芯片数据进行挖掘,为进一步研究AD发生发展机制及寻找潜在的药物治疗靶点提供参考。     

EWSR1‐PBX3 gene fusion in cutaneous syncytial myoepithelioma

Cutaneous syncytial myoepithelioma (CSM) is a recently recognized, histopathological variant of myoepithelial (ME) tumors of the skin. It is characterized by a syncytial arrangement of spindled, ovoid, and/or epithelioid cells forming a well‐circumscribed, unencapsulated dermal nodule. There is a paucity of intervening stroma, and absent duct or gland formation. Strong immunohistochemical staining for S100 and epithelial membrane antigen (EMA) has been described, while cytokeratin expression has been uncommon. The majority of CSMs harbor a rearrangement involving the EWSR1 gene. Although various fusion partner genes have been discovered in ME tumors at other anatomic sites, none has yet been described in CSM. We present a case of CSM represented clinically by a papule on the mid‐upper back of a healthy 44‐year‐old female. It exhibited morphological and immunohistochemical features of a CSM with strong, diffuse S100 and alpha‐actin expression, and focal positivity for EMA and cytokeratin AE1/AE3. Fluorescence in‐situ hybridization showed an EWSR1 gene rearrangement. Massively parallel next‐generation RNA sequencing revealed PBX3 as the fusion partner. The EWSR1‐PBX3 gene fusion has been previously identified in three cases of ME tumors of bone and soft tissue, and in a case of retroperitoneal leiomyoma. This is the first report of an EWSR1‐PBX3 fusion in CSM.