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miR-7 通过靶向多个基因(包括 Skp2 和 Psme3)在 G1/S 期触发细胞周期停滞。

MiR-7 triggers cell cycle arrest at the G1/S transition by targeting multiple genes including Skp2 and Psme3.

机构信息

National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland.

出版信息

PLoS One. 2013 Jun 6;8(6):e65671. doi: 10.1371/journal.pone.0065671. Print 2013.

Abstract

MiR-7 acts as a tumour suppressor in many cancers and abrogates proliferation of CHO cells in culture. In this study we demonstrate that miR-7 targets key regulators of the G1 to S phase transition, including Skp2 and Psme3, to promote increased levels of p27(KIP) and temporary growth arrest of CHO cells in the G1 phase. Simultaneously, the down-regulation of DNA repair-specific proteins via miR-7 including Rad54L, and pro-apoptotic regulators such as p53, combined with the up-regulation of anti-apoptotic factors like p-Akt, promoted cell survival while arrested in G1. Thus miR-7 can co-ordinate the levels of multiple genes and proteins to influence G1 to S phase transition and the apoptotic response in order to maintain cellular homeostasis. This work provides further mechanistic insight into the role of miR-7 as a regulator of cell growth in times of cellular stress.

摘要

miR-7 在许多癌症中充当肿瘤抑制因子,并在培养的 CHO 细胞中阻断增殖。在这项研究中,我们证明 miR-7 靶向 G1 期到 S 期过渡的关键调节因子,包括 Skp2 和 Psme3,以促进 p27(KIP)水平升高,并使 CHO 细胞暂时在 G1 期生长停滞。同时,miR-7 通过下调包括 Rad54L 在内的特定于 DNA 修复的蛋白质和促凋亡调节剂,如 p53,同时上调抗凋亡因子,如 p-Akt,促进细胞在 G1 期停滞时的存活。因此,miR-7 可以协调多个基因和蛋白质的水平,影响 G1 期到 S 期过渡和凋亡反应,以维持细胞内稳态。这项工作为 miR-7 作为细胞应激时细胞生长调节剂的作用提供了进一步的机制见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bd9/3675065/2e34d56716bd/pone.0065671.g001.jpg

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