Regulation of miR-186-YY1 axis by the p53 translational isoform ∆40p53: implications in cell proliferation

ABSTRACT

We have earlier shown that p53-FL and its translational isoform ∆40p53 are differentially regulated. In this study, we have investigated the cellular effect of ∆40p53 regulation on downstream gene expression, specifically miRNAs. Interestingly, ∆40p53 showed antagonistic regulation of miR-186-5p as compared to either p53 alone or a combination of both the isoforms. We have elucidated the miR-186-5p mediated effect of ∆40p53 in cell proliferation. Upon expression of ∆40p53, we observed a significant decrease in YY1 levels, an established target of miR-186-5p, which is involved in cell proliferation. Further assays with anti-miR-186 established the interdependence of ∆40p53− miR-186-5p−YY1− cell proliferation. The results unravel a new dimension toward the understanding of ∆40p53 functions, which seems to regulate cellular fate independent of p53FL.

KEYWORDS:

• P53 isoform
• ∆40p53
• miR-186-5p
• YY1
• cell proliferation

Acknowledgments

We are grateful to Prof. J.C. Bourdon, of the University of Dundee, UK and Dr. Robin Fahraeus, INSERM, France, for providing us the anti-p53 antibody; We acknowledge Dr. Gangi Shetty Subba Rao for providing us the sh RNA against YY1. We also thank the present and past SD lab-members for the helpful discussion of the work. This work is supported by a research grant to SD from the Department of Biotechnology (DBT), Govt. of India. SD also acknowledges the J.C. Bose fellowship for research support. This study was also supported by the DBT-IISc partnership program. DST Fund for Improvement of Science and Technology Infrastructure (FIST) level II infrastructure and University Grants Commission Centre of Advanced Studies support is acknowledged. SKT acknowledges CSIR for fellowship.

Disclosure statement

The authors declare no conflict of interest.

Author contributions

AK and SD: Conception and design of studies. AK, SKT, and AP for analysis, interpretation, writing the article, and performing the experiments.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was supported by the Department of Biotechnology, Ministry of Science and Technology [BT/PR17668/BRB/10/1501/2016]; Department of Biotechnology, Ministry of Science and Technology [DBT-IISc Partnership Program]; Department of Science and Technology, Ministry of Science and Technology [DST FIST]; Science and Engineering Research Board [JC Bose Fellowship] and Council of Scientific and Industrial Research, India [JRF].