Department of Clinical and Molecular Medicine Sapienza University, Sant'Andrea Hospital, Rome, Italy.
J Cell Physiol. 2013 Oct;228(10):2015-23. doi: 10.1002/jcp.24368.
Cell cycle progression is controlled by numerous mechanisms ensuring correct cell division. The transition from one cell cycle phase to another occurs in an orderly fashion and is regulated by different cellular proteins. Therefore an alteration of the regulatory mechanisms of the cell cycle results in uncontrolled cell proliferation, which is a distinctive feature of human cancers. Recent evidences suggest that microRNAs (miRs) may also control the levels of multiple cell cycle regulators and therefore control cell proliferation. In fact miRs are a class of small non-coding RNAs, which modulate gene expression. They are involved in numerous physiological cellular processes and most importantly accumulating evidence indicates that many miRs are aberrantly expressed in human cancers. In this report we describe that miR-24 directly targets p27(Kip1) and p16(Ink4a) in primary keratinocyte and in different cancer derived cell lines promoting their proliferation, suggesting that miR-24 is involved in cyclin-dependent kinase inhibitors post-transcriptional regulation and that upregulation of miR-24 may play a role in carcinogenesis.
细胞周期的进展是由许多机制控制的,这些机制确保了细胞的正确分裂。细胞周期从一个阶段到另一个阶段的转变是有序进行的,并受到不同的细胞蛋白的调节。因此,细胞周期调控机制的改变会导致不受控制的细胞增殖,这是人类癌症的一个显著特征。最近的证据表明,microRNAs(miRs)也可能控制多个细胞周期调节剂的水平,从而控制细胞增殖。事实上,miRs 是一类小的非编码 RNA,可以调节基因表达。它们参与了许多生理细胞过程,最重要的是,越来越多的证据表明,许多 miRs 在人类癌症中异常表达。在本报告中,我们描述了 miR-24 可以直接靶向原代角质形成细胞和不同的癌细胞系中的 p27(Kip1) 和 p16(Ink4a),促进它们的增殖,这表明 miR-24 参与了细胞周期依赖性激酶抑制剂的转录后调节,miR-24 的上调可能在致癌作用中发挥作用。