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Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Jun 10, 2017; 8(3): 178-189
Published online Jun 10, 2017. doi: 10.5306/wjco.v8.i3.178
Histone deacetylases, microRNA and leptin crosstalk in pancreatic cancer
Cynthia I Tchio Mantho, Adriana Harbuzariu, Ruben R Gonzalez-Perez
Cynthia I Tchio Mantho, Adriana Harbuzariu, Ruben R Gonzalez-Perez, Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, United States
Author contributions: Tchio Mantho CI researched and wrote the paper; Harbuzariu A researched and wrote the paper; Gonzalez-Perez RR researched, wrote and edited the paper.
Supported by NIH/NCI, No. 1R41CA183399-01A1; Department of Defense (DoD) office of the Congressionally Directed Medical Research Programs (CDMRP), No. DODXWH-13-1-0382; the DOD W81XWH-13-1-0382; NIH/SBIR1R41CA183399-01A1; Pilot Project Award from MSM/Tuskegee University/UAB Cancer Center Partnership grant 5U54CA118638; PC SPORE Grant from UAB to RRGP; National Institute on Minority Health and Health Disparities (NIMHD) of NIH under award number 5S21MD00101, and facilities and support services at MSM (1G12RR026250-03; NIH RR 03034 and 1C06 RR18386); and The Calvin Johnson Jr. Foundation Pancreatic Cancer Research Scholarship to Cynthia I Tchio Mantho.
Conflict-of-interest statement: The authors declare no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Ruben R Gonzalez-Perez, Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, 720 Westview Drive SW, Hugh Gloster Bldg., Room 329, Atlanta, GA 30310, United States. rgonzalez@msm.edu
Telephone: +1-404-7521581 Fax: +1-404-7521179
Received: January 13, 2017
Peer-review started: January 16, 2017
First decision: February 20, 2017
Revised: March 28, 2017
Accepted: April 18, 2017
Article in press: April 19, 2017
Published online: June 10, 2017
Processing time: 140 Days and 0.2 Hours
Abstract

Because pancreatic cancer (PC) historically has had poor prognosis and five year survival rates, it has been intensely investigated. Analysis of PC incidence and biology has shown a link between different risk factors such as smoking, alcoholism, and obesity and disease progression. Important factors affecting PC include the epigenomic changes driven by DNA methylation and histone acetylation, and actions of microRNA inducing oncogenic or tumor suppressor effects. Studies have identified markers whose dysregulation seem to play important roles in PC progression. PC markers involve classical histone deacetylases (HDAC), PC stem cell (PCSC), and leptin. In this review, we discuss the role of several PC biomarkers, and the potential crosstalk between HDAC, microRNA, and leptin in PC progression. Dysregulated expression of these molecules can increase proliferation, survival, PCSC, resistance to chemotherapy and tumor angiogenesis. The potential relationships between these molecules are further analyzed using data from The Cancer Genome Atlas and crosstalk pathways generated by the Pathway Studio Platform (Ariadne Genomics, Inc.). Oncogenic miRNA21 and tumor suppressor miRNA200 have been previously linked to leptin signaling. Preliminary analysis of PC biopsies and signaling crosstalk suggests that the main adipokine leptin could affect the expression of microRNA and HDAC in PC. Data analysis suggests that HDAC-microRNA-leptin signaling crosstalk may be a new target for PC therapy.

Keywords: Pancreatic Cancer; MicroRNA; Histone deacetylases; Pancreatic cancer stem cell markers; Leptin; Obesity

Core tip: Pancreatic cancer has no targeted therapy. Obesity is a risk factor for pancreatic cancer, characterized by high levels of leptin. In this review, we discuss the potential crosstalk between histone deacetylases, microRNA, and leptin in disease progression. Crosstalk among these molecules increases proliferation, survival, cancer stem cells and resistance to chemotherapy. The potential relationships between these molecules are analyzed using data from the Cancer Genome Atlas and the Pathway Studio Platform. The crosstalk among these molecules could be a novel target for pancreatic cancer prevention or treatment, particularly in obese patients that show elevated levels of leptin.