Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy; Center of Clinical Pathology and Innovative Therapy, I.N.R.C.A. National Institute, Ancona, Italy.
Ageing Res Rev. 2013 Sep;12(4):1056-68. doi: 10.1016/j.arr.2013.05.001. Epub 2013 May 17.
Epidemiological and experimental data demonstrate a strong correlation between age-related chronic inflammation (inflamm-aging) and cancer development. However, a comprehensive approach is needed to clarify the underlying molecular mechanisms. Chronic inflammation has mainly been attributed to continuous immune cells activation, but the cellular senescence process, which may involve acquisition of a senescence-associated secretory phenotype (SASP), can be another important contributor, especially in the elderly. MicroRNAs (miRs), a class of molecules involved in gene expression regulation, are emerging as modulators of some pathways, including NF-κB, mTOR, sirtuins, TGF-β and Wnt, that may be related to inflammation, cellular senescence and age-related diseases, cancer included. Interestingly, cancer development is largely avoided or delayed in centenarians, where changes in some miRs are found in plasma and leukocytes. We identified miRs that can be considered as senescence-associated (SA-miRs), inflammation-associated (inflamma-miRs) and cancer-associated (onco-miRs). Here we review recent findings concerning three of them, miR-21, -126 and -146a, which target mRNAs belonging to the NF-κB pathway; we discuss their ability to link cellular senescence, inflamm-aging and cancer and their changes in centenarians, and provide an update on the possibility of using miRs to block accumulation of senescent cells to prevent formation of a microenvironment favoring cancer development and progression.
流行病学和实验数据表明，与年龄相关的慢性炎症（炎症衰老）与癌症的发展之间存在很强的相关性。然而，需要采用全面的方法来阐明潜在的分子机制。慢性炎症主要归因于持续的免疫细胞激活，但细胞衰老过程（可能涉及获得衰老相关的分泌表型（SASP））也可能是另一个重要的贡献因素，尤其是在老年人中。微小 RNA（miRs）是一类参与基因表达调控的分子，它们作为一些途径的调节剂而崭露头角，包括 NF-κB、mTOR、sirtuins、TGF-β和 Wnt，这些途径可能与炎症、细胞衰老和与年龄相关的疾病（包括癌症）有关。有趣的是，在百岁老人中，癌症的发生在很大程度上被避免或延迟，在他们的血浆和白细胞中发现了一些 miR 的变化。我们鉴定了可以被认为与衰老相关（SA-miRs）、与炎症相关（inflamma-miRs）和与癌症相关（onco-miRs）的 miR。在这里，我们回顾了最近关于 miR-21、-126 和 -146a 的发现，它们靶向属于 NF-κB 途径的 mRNA；我们讨论了它们将细胞衰老、炎症衰老和癌症联系起来的能力，以及它们在百岁老人中的变化，并提供了使用 miR 来阻止衰老细胞积累以防止有利于癌症发展和进展的微环境形成的可能性的最新信息。
