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在大鼠肝癌进展过程中,分选连接蛋白10的下调与miR-30d的过表达相关。

Downregulation of sorting nexin 10 is associated with overexpression of miR-30d during liver cancer progression in rats.

作者信息

Cervantes-Anaya Nancy, Ponciano-Gómez Alberto, López-Álvarez Guadalupe Soledad, Gonzalez-Reyes Christian, Hernández-Garcia Sergio, Cabañas-Cortes María Asunción, Garrido-Guerrero José Efraín, Villa-Treviño Saúl

机构信息

1 Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados (CINVESTAV-IPN), Ciudad de México, México.

2 Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados (CINVESTAV-IPN), Ciudad de México, México.

出版信息

Tumour Biol. 2017 Apr;39(4):1010428317695932. doi: 10.1177/1010428317695932.

Abstract

As of 2012, liver cancer was the second leading cause of death worldwide, and hepatocellular carcinoma is the most common primary cancer of the liver. The identification of molecules that might be molecular markers or therapeutic targets is urgently needed to improve clinical management. Based on a microarray analysis performed in our laboratory, we selected six genes-namely, ANXA2, DYNLT1, PFKP, PLA2G7, KRT19, and SNX10-as candidates for validation as tumor markers of liver cancer in a rat model. Their patterns of overexpression in preneoplastic lesions and established tumors at 10 different time points between 24 h and 18 months were analyzed to identify putative tumor markers for further studies. We validated the microarray results by quantitative reverse transcription polymerase chain reaction, which revealed high transcriptional expression for five of the genes, consistent with their high protein expression during cancer progression reported in the literature. However, studies of the association of sorting nexin 10 with different types of cancer are limited, prompting further study. The characterization of sorting nexin 10 in preneoplastic lesions and established tumors revealed messenger RNA overexpression and a simultaneous decrease in sorting nexin 10 protein expression. A group of microRNAs related to sorting nexin 10 messenger RNA were selected based on a data analysis conducted using miRDB and microrna.org . An analysis of the expression of these microRNAs revealed an increase in the transcription of microRNA-30d whenever the sorting nexin 10 protein was downregulated. These results suggest that sorting nexin 10 is a potential liver cancer marker exhibiting characteristics of a putative suppressor protein that is likely regulated by microRNA-30d.

摘要

截至2012年,肝癌是全球第二大致死原因,而肝细胞癌是肝脏最常见的原发性癌症。迫切需要鉴定可能作为分子标志物或治疗靶点的分子,以改善临床管理。基于我们实验室进行的微阵列分析,我们选择了六个基因,即膜联蛋白A2(ANXA2)、动力蛋白轻链T1(DYNLT1)、磷酸果糖激酶P(PFKP)、磷脂酶A2G7(PLA2G7)、角蛋白19(KRT19)和分选连接蛋白10(SNX10),作为在大鼠模型中验证为肝癌肿瘤标志物的候选基因。分析了它们在癌前病变和已形成肿瘤中在24小时至18个月的10个不同时间点的过表达模式,以鉴定用于进一步研究的推定肿瘤标志物。我们通过定量逆转录聚合酶链反应验证了微阵列结果,该结果显示其中五个基因具有高转录表达,这与文献报道的它们在癌症进展过程中的高蛋白表达一致。然而,关于分选连接蛋白10与不同类型癌症关联的研究有限,这促使进一步研究。对癌前病变和已形成肿瘤中分选连接蛋白10的表征显示信使核糖核酸过表达,同时分选连接蛋白10蛋白表达下降。基于使用miRDB和microrna.org进行的数据分析,选择了一组与分选连接蛋白10信使核糖核酸相关的微小核糖核酸。对这些微小核糖核酸表达的分析显示,每当分选连接蛋白10蛋白下调时,微小核糖核酸-30d的转录就会增加。这些结果表明,分选连接蛋白10是一种潜在的肝癌标志物,表现出可能受微小核糖核酸-30d调控的推定抑制蛋白的特征。

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