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长链非编码 RNA NEAT1 在女性癌症发病机制中的作用概述;从诊断到治疗抵抗。

An overview of lncRNA NEAT1 contribution in the pathogenesis of female cancers; from diagnosis to therapy resistance.

机构信息

Electronic Marketing and Social Media, Economic and Administrative Sciences Zarqa University, Jordan; Research follower, INTI International University, 71800 Negeri Sembilan, Malaysia.

Medical Laboratory Techniques Department, College of Health and Medical Technology, University of Al-maarif, Anbar, Iraq.

出版信息

Gene. 2025 Jan 15;933:148975. doi: 10.1016/j.gene.2024.148975. Epub 2024 Sep 29.

Abstract

Despite the ongoing progress in detecting and treating cancer, there is still a need for extensive research into the molecular mechanisms involved in the emergence, progression, and resistance to recurrence of female reproductive tissue-specific cancers such as ovarian, breast, cervical, and endometrial cancers. The nuclear paraspeckle assembly transcript 1 (NEAT1) is a long non-coding RNA (lncRNA) that exhibits increased expression in female tumors. Moreover, elevated levels of NEAT1 have been associated with poorer survival outcomes in cancer patients. NEAT1 plays a pivotal role in driving tumor initiation through modulating the expression of genes involved in various aspects of tumor cell proliferation, epithelial-to-mesenchymal transition (EMT), metastasis, chemoresistance, and radio-resistance. Mechanistically, NEAT1 acts as a scaffold RNA molecule via interacting with EZH2 (Enhancer of Zeste 2 Polycomb Repressive Complex 2 Subunit), thereby influencing the expression of downstream effectors of EZH2. Additionally, NEAT1 functions as a competing endogenous RNA (ceRNA) by microRNAs (miRNAs) sponging, consequently altering the expression levels of their target genes during the development of female cancers. This comprehensive review aims to shed light on the latest insights regarding the expression pattern, biological functions, and underlying mechanisms governing the function and regulation of NEAT1 in tumors. Furthermore, particular emphasis is placed on its clinical significance as a novel diagnostic biomarker and a promising therapeutic target for female cancers.

摘要

尽管在癌症的检测和治疗方面不断取得进展,但仍需要广泛研究女性生殖组织特异性癌症(如卵巢癌、乳腺癌、宫颈癌和子宫内膜癌)的发生、进展和对复发的抵抗的分子机制。核斑蛋白组装转录本 1(NEAT1)是一种长链非编码 RNA(lncRNA),在女性肿瘤中表达增加。此外,NEAT1 水平升高与癌症患者的生存结局较差有关。NEAT1 通过调节与肿瘤细胞增殖、上皮间质转化(EMT)、转移、化疗耐药和放射耐药等各个方面相关的基因的表达,在驱动肿瘤发生中发挥关键作用。从机制上讲,NEAT1 作为一种支架 RNA 分子与 EZH2( Enhancer of Zeste 2 Polycomb Repressive Complex 2 Subunit)相互作用,从而影响 EZH2 的下游效应物的表达。此外,NEAT1 作为竞争性内源 RNA(ceRNA)通过 microRNAs(miRNAs)海绵作用,在女性癌症的发展过程中改变其靶基因的表达水平。这篇综述旨在阐明有关 NEAT1 在肿瘤中的表达模式、生物学功能以及调控机制的最新见解。此外,特别强调了其作为女性癌症新型诊断生物标志物和有前途的治疗靶点的临床意义。

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