Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, China.
The 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing, 400044, China.
Acta Pharmacol Sin. 2021 Nov;42(11):1888-1899. doi: 10.1038/s41401-020-00599-9. Epub 2021 Feb 1.
Pre-B-cell leukemia transcription factor 3 (PBX3) is a member of the PBX family and contains a highly conserved homologous domain. PBX3 is involved in the progression of gastric cancer, colorectal cancer, and prostate cancer; however, the detailed mechanism by which it promotes tumor growth remains to be elucidated. Here, we found that PBX3 silencing induces the expression of the cell cycle regulator p21, leading to an increase in colorectal cancer (CRC) cell apoptosis as well as suppression of proliferation and colony formation. Furthermore, we found that PBX3 is highly expressed in clinical CRC patients, in whom p21 expression is aberrantly low. We found that the regulation of p21 transcription by PBX3 occurs through the upstream regulator of p21, the tumor suppressor p53, as PBX3 binds to the p53 promoter and suppresses its transcriptional activity. Finally, we revealed that PBX3 regulates tumor growth through regulation of the p53/p21 axis. Taken together, our results not only describe a novel mechanism regarding PBX3-mediated regulation of tumor growth but also provide new insights into the regulatory mechanism of the tumor suppressor p53.
前 B 细胞白血病转录因子 3（PBX3）是 PBX 家族的成员，含有高度保守的同源结构域。PBX3 参与胃癌、结直肠癌和前列腺癌的进展；然而，其促进肿瘤生长的详细机制仍有待阐明。在这里，我们发现 PBX3 沉默诱导细胞周期调节剂 p21 的表达，导致结直肠癌细胞（CRC）凋亡增加以及增殖和集落形成受到抑制。此外，我们发现 PBX3 在临床 CRC 患者中高度表达，其中 p21 的表达异常降低。我们发现 PBX3 通过 p21 的上游调节因子，肿瘤抑制因子 p53，对 p21 转录的调节发生，因为 PBX3 结合到 p53 启动子并抑制其转录活性。最后，我们揭示 PBX3 通过调节 p53/p21 轴来调节肿瘤生长。总之，我们的结果不仅描述了 PBX3 介导的肿瘤生长调控的新机制，而且为肿瘤抑制因子 p53 的调节机制提供了新的见解。
