Article

The transcription factor PBX3 promotes tumor cell growth through transcriptional suppression of the tumor suppressor p53

Wen-fang Li1,2, Arin Herkilini1,2, Yu Tang1, Ping Huang1, Guan-bin Song1,2, Makoto Miyagishi3, Vivi Kasim1,2,4, Shou-rong Wu1,2,4
1 Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
2 The 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China
3 Molecular Composite Medicine Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan
4 Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing University, Chongqing 400030, China
Correspondence to: Vivi Kasim: vivikasim@cqu.edu.cn, Shou-rong Wu: shourongwu@cqu.edu.cn,
DOI: 10.1038/s41401-020-00599-9
Received: 4 September 2020
Accepted: 15 December 2020
Advance online: 1 February 2021

Abstract

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.
Keywords: Pre-B-cell leukemia transcription factor 3 (PBX3); p53; cyclin-dependent kinase inhibitor p21; apoptosis; cell proliferation

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