Research Papers:

MiR-766 induces p53 accumulation and G2/M arrest by directly targeting MDM4

Qingqing Wang, Luke A. Selth and David F. Callen _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2017; 8:29914-29924. https://doi.org/10.18632/oncotarget.15530

Metrics: PDF 1571 views  |   HTML 1719 views  |   ?  


Qingqing Wang1, Luke A. Selth2,3 and David F. Callen1

1Breast Cancer Genetics Group, Centre for Personalised Cancer Medicine, School of Medicine, University of Adelaide, Adelaide, South Australia

2Dame Roma Mitchell Cancer Research Laboratories, School of Medicine, University of Adelaide, Adelaide, South Australia

3Freemasons Foundation Centre for Men’s Health, Discipline of Medicine, University of Adelaide, Adelaide, South Australia

Correspondence to:

David F. Callen, email: [email protected]

Luke A. Selth, email: [email protected]

Keywords: MicroRNA, MDM4, p53, cancer, cell cycle

Received: June 30, 2016    Accepted: January 31, 2017    Published: February 20, 2017


p53, a transcription factor that participates in multiple cellular functions, is considered the most important tumor suppressor. Previous evidence suggests that post-transcriptional deregulation of p53 by microRNAs contributes to tumorigenesis, tumor progression and therapeutic resistance. In the present study, we found that the microRNA miR-766 was aberrantly expressed in breast cancer, and that over-expression of miR-766 caused accumulation of wild-type p53 protein in multiple cancer cell lines. Supporting its role in the p53 signalling pathway, miR-766 decreased cell proliferation and colony formation in several cancer cell lines, and cell cycle analyses revealed that miR-766 causes G2 arrest. At a mechanistic level, we demonstrate that miR-766 enhances p53 signalling by directly targeting MDM4, an oncogene and negative regulator of p53. Analysis of clinical genomic data from multiple cancer types supports the relevance of miR-766 in p53 signalling. Collectively, our study demonstrates that miR-766 can function as a novel tumor suppressor by enhancing p53 signalling.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 15530