The "LINC" between Δ40p53-miRNA Axis in the Regulation of Cellular Homeostasis.

IF 3.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular and Cellular Biology Pub Date : 2023-01-01 Epub Date: 2023-06-07 DOI:10.1080/10985549.2023.2213147

Apala Pal, Pritam Kumar Ghosh, Saumitra Das

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引用次数: 0

Abstract

Previous research has shown that Δ40p53, the translational isoform of p53, can inhibit cell growth independently of p53 by regulating microRNAs. Here, we explored the role of Δ40p53 in regulating the long noncoding RNA-micro-RNA-cellular process axis, specifically focusing on LINC00176. Interestingly, LINC00176 levels were predominantly affected by the overexpression/stress-mediated induction and knockdown of Δ40p53 rather than p53 levels. Additional assays revealed that Δ40p53 transactivates LINC00176 transcriptionally and could also regulate its stability. RNA immunoprecipitation experiments revealed that LINC00176 sequesters several putative microRNA targets, which could further titrate several mRNA targets involved in different cellular processes. To understand the downstream effects of this regulation, we ectopically overexpressed and knocked down LINC00176 in HCT116 p53-/- (harboring only Δ40p53) cells, which affected their proliferation, cell viability, and expression of epithelial markers. Our results provide essential insights into the pivotal role of Δ40p53 in regulating the novel LINC00176 RNA-microRNA-mRNA axis independent of FL-p53 and in maintaining cellular homeostasis.

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细胞稳态调节中Δ40p53-miRNA 轴之间的 "LINC"。

以往的研究表明，p53的翻译异构体Δ40p53可以通过调节微RNA抑制细胞生长，而不依赖于p53。在这里，我们探讨了Δ40p53在调控长非编码RNA-微RNA-细胞过程轴中的作用，特别关注了LINC00176。有趣的是，LINC00176水平主要受Δ40p53过表达/应激诱导和敲除的影响，而不是p53水平。其他实验表明，Δ40p53能转录激活LINC00176，也能调节其稳定性。RNA 免疫沉淀实验显示，LINC00176 可封存多个推测的 microRNA 靶点，从而进一步滴定参与不同细胞过程的多个 mRNA 靶点。为了了解这种调控的下游效应，我们在 HCT116 p53-/-（仅携带 Δ40p53）细胞中异位过表达和敲除了 LINC00176，这影响了它们的增殖、细胞活力和上皮标志物的表达。我们的研究结果为我们深入了解Δ40p53在独立于FL-p53调控新型LINC00176 RNA-microRNA-mRNA轴以及维持细胞稳态方面的关键作用提供了重要启示。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular and Cellular Biology 生物-生化与分子生物学

CiteScore

9.80

自引率

1.90%

发文量

120

审稿时长

1 months

期刊介绍： Molecular and Cellular Biology (MCB) showcases significant discoveries in cellular morphology and function, genome organization, regulation of genetic expression, morphogenesis, and somatic cell genetics. The journal also examines viral systems, publishing papers that emphasize their impact on the cell.