Andonegui-Elguera Marco A, Cáceres-Gutiérrez Rodrigo E, Oliva-Rico Diego, Díaz-Chávez José, Herrera Luis A
Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas-Universidad Nacional Autónoma de México, Instituto Nacional de Cancerología, México City, Mexico.
Instituto Nacional de Medicina Genómica, Mexico City, Mexico.
Front Genet. 2022 Nov 21;13:984329. doi: 10.3389/fgene.2022.984329. eCollection 2022.
Although a large part of the genome is transcribed, only 1.9% has a protein-coding potential; most of the transcripts are non-coding RNAs such as snRNAs, tRNAs, and rRNAs that participate in mRNA processing and translation. In addition, there are small RNAs with a regulatory role, such as siRNAs, miRNAs, and piRNAs. Finally, the long non-coding RNAs (lncRNAs) are transcripts of more than 200 bp that can positively and negatively regulate gene expression (both in cis and trans), serve as a scaffold for protein recruitment, and control nuclear architecture, among other functions. An essential process regulated by lncRNAs is genome stability. LncRNAs regulate genes associated with DNA repair and chromosome segregation; they are also directly involved in the maintenance of telomeres and have recently been associated with the activity of the centromeres. In cancer, many alterations in lncRNAs have been found to promote genomic instability, which is a hallmark of cancer and is associated with resistance to chemotherapy. In this review, we analyze the most recent findings of lncRNA alterations in cancer, their relevance in genomic instability, and their impact on the resistance of tumor cells to anticancer therapy.
尽管基因组的很大一部分都被转录,但只有1.9%具有蛋白质编码潜力;大多数转录本是非编码RNA,如参与mRNA加工和翻译的snRNA、tRNA和rRNA。此外,还有具有调控作用的小RNA,如siRNA、miRNA和piRNA。最后,长链非编码RNA(lncRNA)是长度超过200 bp的转录本,可正向和负向调控基因表达(顺式和反式),作为蛋白质募集的支架,并控制核结构等。lncRNA调控的一个重要过程是基因组稳定性。lncRNA调控与DNA修复和染色体分离相关的基因;它们也直接参与端粒的维持,最近还与着丝粒的活性有关。在癌症中,已发现lncRNA的许多改变会促进基因组不稳定,这是癌症的一个标志,并且与化疗耐药性相关。在本综述中,我们分析了癌症中lncRNA改变的最新发现、它们在基因组不稳定中的相关性以及它们对肿瘤细胞抗癌治疗耐药性的影响。