Leptin induction following irradiation is a conserved feature in mammalian epithelial cells and tissues

Abstract

Purpose: Leptin (LEP) is a peptide hormone with multiple physiological functions. Besides its systemic actions, it has important peripheral roles such as a mitogen action on keratinocytes following skin lesions. We previously showed that LEP mRNA is significantly induced in response to neutron irradiation in mouse skin and that the protein increases in the irradiated epidermis and in the related subcutaneous adipose tissue. In this work, we investigated the post-transcriptional regulation of LEP by miRNAs and the conservation of LEP’s role in radiation response in human cells.

Methods: We used microarray analysis and real-time polymerase chain reaction (RT-PCR) to analyze modulation of miRNAs potentially targeting LEP in mouse skin following irradiation and bioinformatic analysis of transcriptome of irradiated human cell lines and cancer tissues from radiotherapy-treated patients to evaluate LEP expression.

Results and conclusions: We show that a network of miRNAs potentially targeting LEP mRNA is modulated in irradiated mouse skin and that LEP itself is significantly modulated by irradiation in human epithelial cell lines and in breast cancer tissues from radiotherapy-treated patients. These results confirm and extend the previous evidence that LEP has a general and important role in the response of mammalian cells to irradiation.

Keywords:

• Leptin
• ionizing radiation
• radiotherapy
• miRNA
• transcriptional response to irradiation

Acknowledgements

We thank Dr. Emiliano Fratini for helpful suggestions and technical work.

Disclosure statement

No potential conflict of interest was reported by the authors.

Notes on Contributors

Valerio Licursi Postdoctoral fellow, Institute for Systems Analysis and Computer Science "Antonio Ruberti", National Research Council, Rome, Italy. Dr. Licursi gained his PhD in Cellular and Developmental Biology from the ?Sapienza?, University of Rome. He has knowledge of molecular biology and bioinformatics focusing on epigenetics and gene expression interaction.

Mariangela Cestelli Guidi Research Scientist at National Institute for Nuclear Physics (INFN) and Synchrotron Infrared beamline coordinator at INFN Laboratori Nazionali di Frascati. Research activity focused on Infrared Spectroscopy in life science.

Giorgia Del Vecchio Postdoctoral fellow, Department of Biology and Biotechnology “C. Darwin”, Sapienza University of Rome. CV and research activity: http://bbcd.bio.uniroma1.it/bbcd/sites/default/files/Del%20Vecchio_CV.pdf

Cecilia Mannironi Research Scientist at the National Research Council of Italy. Dr. Mannironi is a molecular biologist, with a general research interest on the role of epigenetic mechanisms involved in the control of gene expression during stress response. CV at: https://www.ibpm.cnr.it/index.php?option=com_cnr&view=profile&id=550&lang=en

Carlo Presutti Associate Professor of Molecular Biology. The lab is focalized on RNA structure and function in eukaryotic cells. CV and research activity: http://bbcd.bio.uniroma1.it/bbcd/users/presutti

Roberto Amendola Senior Scientist at ENEA, formerly National Italian Agency for Nuclear research, and INFN, Institute of National Nuclear Physics. Lecturer at the National Nuclear Research University of Moscow (RU).

Rodolfo Negri Full professor of Molecular Biology and responsible for the Laboratory of Functional Genomics and Proteomics of Model Systems of Sapienza University of Rome. CV and research activity: http://bbcd.bio.uniroma1.it/bbcd/users/negri-rodolfo

Additional information

Funding

This work was supported by INFN (Grant CNS-V-ETHICS-2015-1017) and by funds from Sapienza Università di Roma (Grant: C26A158CE3).