MiR-377 Reverses Cancerous Phenotypes of Pancreatic Cells Via Suppressing DNMT1 and Demethylating Tumor Suppressor Genes

Abstract

Aim: The aim was to investigate the effect of miR-377 on DNMT1 expression and cancer phenotype in pancreatic cancer cells. Materials & methods: Real-time PCR, luciferase assay, MTT and Annexin-PI staining were used. Results: Decreased miR-377 and increased DNMT1 (verified as a target for mir-377) levels in pancreatic cancer tissues and cell lines in comparison with normal tissues was confirmed to be influenced by promoter methylation. Also hypermethylation of BNIP3, SPARC, TFPI2 and PENK promoters was observed in tumor samples but not in normal tissues which negatively correlated with their expression. Restoration of miR-377 resulted in a reduction of the expression of DNMT1 and reactivation of BNIP3 and SPARC genes via promoter demethylation. Furthermore, enhanced expression of miR-377 could significantly inhibit cell proliferation and induce apoptosis. Conclusion: Our findings showed that miR-377 through targeting DNMT1 could reduce DNA methylation of some tumor suppressor genes and restore their expression in pancreatic cancer cells.

Keywords::

• DNA (cytosine-5-)-methyltransferase 1
• epigenetics
• genes
• human
• methylation
• MIRN377
• microRNA
• neoplasm
• pancreatic neoplasms
• tumor suppressor

Acknowledgements

The authors thank the patients and clinicians contributing to this study. Also the authors thank Virology Department staffs for providing us the equipment.

Financial & competing interest disclosure

This research was funded by the Pasteur Institute of Iran. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

Informed written consent had been obtained from each patient before obtaining the samples which was approved by ethics committee of Pasteur Institute of Iran.

Additional information

Funding

This research was funded by the Pasteur Institute of Iran. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.