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微小RNA和小干扰RNA在子宫颈癌发生中的作用

Utility of microRNAs and siRNAs in cervical carcinogenesis.

作者信息

Díaz-González Sacnite del Mar, Deas Jessica, Benítez-Boijseauneau Odelia, Gómez-Cerón Claudia, Bermúdez-Morales Victor Hugo, Rodríguez-Dorantes Mauricio, Pérez-Plasencia Carlos, Peralta-Zaragoza Oscar

机构信息

Direction of Chronic Infections and Cancer, Research Center in Infection Diseases, National Institute of Public Health, Avenida Universidad No. 655, Cerrada los Pinos y Caminera, Colonia Santa María Ahuacatitlán, 62100 Cuernavaca, MOR, Mexico.

National Institute of Genomic Medicine, Periférico Sur No. 4809, Colonia Arenal Tepepan, Delegación Tlalpan, 14610 Mexico City, DF, Mexico.

出版信息

Biomed Res Int. 2015;2015:374924. doi: 10.1155/2015/374924. Epub 2015 Mar 22.

Abstract

MicroRNAs and siRNAs belong to a family of small noncoding RNAs which bind through partial sequence complementarity to 3'-UTR regions of mRNA from target genes, resulting in the regulation of gene expression. MicroRNAs have become an attractive target for genetic and pharmacological modulation due to the critical function of their target proteins in several signaling pathways, and their expression profiles have been found to be altered in various cancers. A promising technology platform for selective silencing of cell and/or viral gene expression using siRNAs is currently in development. Cervical cancer is the most common cancer in women in the developing world and sexually transmitted infection with HPV is the cause of this malignancy. Therefore, a cascade of abnormal events is induced during cervical carcinogenesis, including the induction of genomic instability, reprogramming of cellular metabolic pathways, deregulation of cell proliferation, inhibition of apoptotic mechanisms, disruption of cell cycle control mechanisms, and alteration of gene expression. Thus, in the present review article, we highlight new research on microRNA expression profiles which may be utilized as biomarkers for cervical cancer. Furthermore, we discuss selective silencing of HPV E6 and E7 with siRNAs which represents a potential gene therapy strategy against cervical cancer.

摘要

微小RNA(miRNA)和小干扰RNA(siRNA)属于一类小的非编码RNA,它们通过部分序列互补与靶基因mRNA的3'-非翻译区(3'-UTR)结合,从而调控基因表达。由于其靶蛋白在多种信号通路中具有关键功能,miRNA已成为基因和药物调控的一个有吸引力的靶点,并且已发现其表达谱在各种癌症中发生改变。目前正在开发一种利用siRNA选择性沉默细胞和/或病毒基因表达的有前景的技术平台。宫颈癌是发展中国家女性中最常见的癌症,人乳头瘤病毒(HPV)的性传播感染是这种恶性肿瘤的病因。因此,在宫颈癌发生过程中会诱导一系列异常事件,包括基因组不稳定的诱导、细胞代谢途径的重编程、细胞增殖的失调、凋亡机制的抑制、细胞周期控制机制的破坏以及基因表达的改变。因此,在本综述文章中,我们重点介绍了关于miRNA表达谱的新研究,这些研究可能被用作宫颈癌的生物标志物。此外,我们讨论了用siRNA选择性沉默HPV E6和E7,这代表了一种针对宫颈癌的潜在基因治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c60/4385600/df42e2934921/BMRI2015-374924.001.jpg

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