Biomedical Engineering Department, College of Engineering.
Biomedical Engineering Department, College of Engineering State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Molecular Medicine, Peking University, Beijing, 100871, China.
RNA. 2014 Jun;20(6):765-72. doi: 10.1261/rna.043026.113. Epub 2014 Apr 17.
Tumor suppressor TP53 (or p53) is one of the most important regulators in numerous physiological and pathological processes. Recently, the miRNA-mediated post-transcription regulation of p53 has been studied. However, systematic studies of miRNA targeting sites within the p53 gene are still a challenging task. Here, we developed a dual-color assay capable of identifying miRNA targeting sites in a certain gene, specifically p53, in a simple, direct, and robust manner. Results showed that p53 was a direct and critical target of miR-19b, but not miR-19a, regardless of sequence similarity. Overexpression of miR-19b observed in human cancer cells can diminish p53 protein levels and, subsequently, downstream components such as Bax and p21. This miR-19b-mediated p53 reduction was shown to promote cell cycle, cell migration or invasion, and repress senescence and apoptosis in vitro. Further investigation revealed that miR-19b controls tumor growth and metastasis in vivo. Therefore, it is possible that miR-19b antagomirs or sponges could be developed as therapeutic agents against tumor development.
肿瘤抑制因子 TP53（或 p53）是众多生理和病理过程中最重要的调节因子之一。最近，研究人员研究了 miRNA 介导的 p53 转录后调控。然而，对 p53 基因内 miRNA 靶向位点的系统研究仍然是一项具有挑战性的任务。在这里，我们开发了一种双色测定法，能够以简单、直接和稳健的方式鉴定特定基因（特别是 p53）中的 miRNA 靶向位点。结果表明，miR-19b 可以直接靶向 p53，而 miR-19a 则不能，无论序列是否相似。在人类癌细胞中观察到的 miR-19b 的过表达可以降低 p53 蛋白水平，进而降低 Bax 和 p21 等下游成分。这种 miR-19b 介导的 p53 减少被证明可以促进细胞周期、细胞迁移或侵袭，并抑制体外衰老和凋亡。进一步的研究表明，miR-19b 可以控制体内肿瘤的生长和转移。因此，开发 miR-19b 拮抗剂或海绵可能成为治疗肿瘤发展的治疗剂。
