Analytical Biochemistry Unit, Nuclear Research Center, School of Science, Universidad de la República, Montevideo 11400, Uruguay.
Functional Genomics Unit, Institut Pasteur de Montevideo, Montevideo 11400, Uruguay.
RNA. 2021 Apr;27(4):403-410. doi: 10.1261/rna.078444.120. Epub 2020 Dec 29.
There is increasing interest among cancer researchers in the study of Piwi-interacting RNAs (piRNAs), a group of small RNAs important for maintaining genome stability in the germline. Aberrant expression of piRNAs in cancer could imply an involvement of these regulatory RNAs in neoplastic transformation. On top of that, it could enable early cancer diagnosis based on RNA analysis in liquid biopsies, as piRNAs are not expected to widely circulate in the bloodstream of healthy individuals. Indeed, it has recently been shown that serum piR-54265 allows for excellent discrimination between colorectal cancer patients and healthy controls. However, we have also shown that most somatic piRNAs reported to date in mammals are actually fragments of other noncoding RNAs. Herein, we show that reports positioning piR-54265 as a noninvasive biomarker for colorectal cancer were actually measuring variations in the levels of a full-length (72 nt) small nucleolar RNA in serum. This should place a cautionary note for future research in somatic and cancer-specific piRNAs. We deeply encourage this line of research but discuss proper ways to identify somatic piRNAs without the interference of erroneous entries contained in piRNA databases. We also introduce the concept of miscellaneous-piRNAs (m-piRNAs) to distinguish between canonical piRNAs and other small RNAs circumstantially associated with PIWI proteins in somatic cells.
癌症研究人员越来越关注 Piwi 相互作用 RNA(piRNAs)的研究,piRNAs 是一组在生殖系中维持基因组稳定性的重要小 RNA。piRNA 在癌症中的异常表达可能意味着这些调节 RNA 参与了肿瘤转化。除此之外,它还可以通过液体活检中的 RNA 分析实现早期癌症诊断,因为健康个体的血液中不应广泛存在 piRNAs。事实上,最近已经表明,血清 piR-54265 可以极好地区分结直肠癌患者和健康对照者。然而,我们还表明,迄今为止在哺乳动物中报道的大多数体细胞 piRNAs 实际上是其他非编码 RNA 的片段。在此,我们表明,将 piR-54265 定位为结直肠癌无创生物标志物的报告实际上是在测量血清中全长(72nt)小核仁 RNA 水平的变化。这应该为体细胞和癌症特异性 piRNAs 的未来研究敲响警钟。我们非常鼓励这一研究方向,但我们也讨论了在不干扰 piRNA 数据库中包含的错误条目情况下,正确识别体细胞 piRNAs 的方法。我们还引入了杂合 piRNAs(m-piRNAs)的概念,以区分体细胞中与 PIWI 蛋白偶然相关的典型 piRNAs 和其他小 RNA。