Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India.
National Institute of Biomedical Genomics, Kalyani, India.
Cell Cycle. 2021 Mar-Mar;20(5-6):561-574. doi: 10.1080/15384101.2021.1875670. Epub 2021 Feb 25.
We have earlier shown that p53-FL and its translational isoform ∆40p53 are differentially regulated. In this study, we have investigated the cellular effect of ∆40p53 regulation on downstream gene expression, specifically miRNAs. Interestingly, ∆40p53 showed antagonistic regulation of miR-186-5p as compared to either p53 alone or a combination of both the isoforms. We have elucidated the miR-186-5p mediated effect of ∆40p53 in cell proliferation. Upon expression of ∆40p53, we observed a significant decrease in YY1 levels, an established target of miR-186-5p, which is involved in cell proliferation. Further assays with anti-miR-186 established the interdependence of ∆40p53- miR-186-5p-YY1- cell proliferation. The results unravel a new dimension toward the understanding of ∆40p53 functions, which seems to regulate cellular fate independent of p53FL.
我们之前已经表明，p53-FL 及其翻译后异构体 ∆40p53 的表达受到不同的调控。在这项研究中，我们研究了 ∆40p53 对下游基因表达（特别是 microRNA）的细胞效应的调节。有趣的是，与单独的 p53 或两种异构体的组合相比，∆40p53 对 miR-186-5p 的调节表现出拮抗作用。我们阐明了 ∆40p53 在细胞增殖中对 miR-186-5p 的介导作用。表达 ∆40p53 后，我们观察到 YY1 水平显著降低，YY1 是 miR-186-5p 的一个已确定靶点，参与细胞增殖。用抗 miR-186 进行的进一步检测确立了 ∆40p53-miR-186-5p-YY1-细胞增殖之间的相互依存关系。这些结果揭示了对 ∆40p53 功能的理解的一个新维度，它似乎独立于 p53FL 调节细胞命运。
