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Mir-377 Reverses Cancerous Phenotypes of Pancreatic Cells Via Suppressing Dnmt1 and Demethylating Tumor Suppressor Genes Publisher Pubmed



Azizi M1 ; Fardesfahani P2 ; Mahmoodzadeh H3 ; Fazeli MS4 ; Azadmanesh K5 ; Zeinali S1 ; Teimooritoolabi L1
Authors
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Authors Affiliations
  1. 1. Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
  2. 2. Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran
  3. 3. Cancer Institute of Iran, Imam Khomeini Medical Complex, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Surgery, Division of Colo-Rectal Surgery, Imam Khomeini Medical Complex, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Virology Department, Pasteur Institute of Iran, Tehran, Iran

Source: Epigenomics Published:2017


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. © 2017 Future Medicine Ltd.
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