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[RNA干扰:生物发生、分子机制及其在宫颈癌中的应用]

[RNA interference: biogenesis molecular mechanisms and its applications in cervical cancer].

作者信息

Peralta-Zaragoza Oscar, Bermúdez-Morales Víctor Hugo, Madrid-Marina Vicente

机构信息

Dirección de Infecciones Crónicas y Cáncer, Institute Nacional de Salud Pública.

出版信息

Rev Invest Clin. 2010 Jan-Feb;62(1):63-80.

Abstract

RNAi (RNA interference) is a natural process by which eukaryotic cells silence gene expression through small interference RNAs (siRNA) which are complementary to messenger RNA (mRNA). In this process, the siRNA that are 21-25 nucleotides long and are known as microRNA (miRNA), either associate with the RNA-induced silencing complex (RISC), which targets and cleaves the complementary mRNAs by the endonucleolytic pathway, or repress the translation. It is also possible to silence exogenous gene expression during viral infections by using DNA templates to transcribe siRNA with properties that are identical to those of bioactive microRNA. Persistent human papillomavirus (HPV) infection is the main etiological agent during cervical cancer development and the HPV E6 and E7 oncogenes, which induce cellular transformation and immortalization, represent strategic targets to be silenced with siRNA. In several in vitro and in vivo studies, it has been demonstrated that the introduction of siRNA directed against the E6 and E7 oncogenes in human tumoral cervical cells transformed by HPV, leads to the efficient silencing of HPV E6 and E7 oncogene expression, which induces the accumulation of the products of the p53 and pRb tumor suppressor genes and activates the mechanism of programmed cell death by apoptosis; thus, the progression of the tumoral growth process may be prevented. The goal of this review is to analyze the microRNA biogenesis process in the silencing of gene expression and to discuss the different protocols for the use of siRNA as a potential gene therapy strategy for the treatment of cervical cancer.

摘要

RNA干扰(RNAi)是一种自然过程,通过该过程,真核细胞利用与信使RNA(mRNA)互补的小干扰RNA(siRNA)使基因表达沉默。在这个过程中,长度为21 - 25个核苷酸的siRNA,即微小RNA(miRNA),要么与RNA诱导沉默复合体(RISC)结合,RISC通过核酸内切酶途径靶向并切割互补的mRNA,要么抑制翻译。在病毒感染期间,也可以通过使用DNA模板转录具有与生物活性微小RNA相同特性的siRNA来使外源基因表达沉默。持续性人乳头瘤病毒(HPV)感染是宫颈癌发生过程中的主要病因,而HPV的E6和E7癌基因可诱导细胞转化和永生化,是用siRNA使其沉默的战略靶点。在多项体外和体内研究中已证明,将针对E6和E7癌基因的siRNA导入由HPV转化的人宫颈肿瘤细胞中,可有效沉默HPV E6和E7癌基因的表达,这会诱导p53和pRb肿瘤抑制基因产物的积累,并通过凋亡激活程序性细胞死亡机制;因此,可以阻止肿瘤生长过程的进展。本综述的目的是分析基因表达沉默过程中的微小RNA生物合成过程,并讨论将siRNA用作治疗宫颈癌的潜在基因治疗策略的不同方案。

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