A microRNA/Runx1/Runx2 network regulates prostate tumor progression from onset to adenocarcinoma in TRAMP mice.

Authors

Nicholas H Farina, Department of Biochemistry and University of Vermont Cancer Center, University of Vermont College of Medicine
Areg Zingiryan, Department of Biochemistry and University of Vermont Cancer Center, University of Vermont College of Medicine
Jacqueline A Akech, Department of Cell and Developmental Biology, University of Massachusetts Medical SchoolFollow
Cody J Callahan, Department of Biochemistry and University of Vermont Cancer Center, University of Vermont College of Medicine
Huimin Lu, Prostate Cancer Discovery and Development Program; Thomas Jefferson University, PhiladelphiaFollow
Janet L Stein, Department of Biochemistry and University of Vermont Cancer Center, University of Vermont College of Medicine
Lucia R Languino, Department of Cancer Biology, Prostate Cancer Discovery and Development Program, Thomas Jefferson UniversityFollow
Gary S Stein, Department of Biochemistry and University of Vermont Cancer Center, University of Vermont College of MedicineFollow
Jane B Lian, Department of Biochemistry and University of Vermont Cancer Center, University of Vermont College of MedicineFollow

Document Type

Article

Publication Date

9-13-2016

Comments

This article has been peer reviewed. It was published in: Oncotarget.
Volume 7, Issue 43, 2016, Pages 70462-70474.
The published version is available at DOI: 10.18632/oncotarget.11992

Copyright © 2016 The Authors

Abstract

While decades of research have identified molecular pathways inducing and promoting stages of prostate cancer malignancy, studies addressing dynamic changes of cancer-related regulatory factors in a prostate tumor progression model are limited. Using the TRAMP mouse model of human prostate cancer, we address mechanisms of deregulation for the cancer-associated transcription factors, Runx1 and Runx2 by identifying microRNAs with reciprocal expression changes at six time points during 33 weeks of tumorigenesis. We molecularly define transition stages from PIN lesions to hyperplasia/neoplasia and progression to adenocarcinoma by temporal changes in expression of human prostate cancer markers, including the androgen receptor and tumor suppressors, Nkx3.1 and PTEN. Concomitant activation of PTEN, AR, and Runx factors occurs at early stages. At late stages, PTEN and AR are downregulated, while Runx1 and Runx2 remain elevated. Loss of Runx-targeting microRNAs, miR-23b-5p, miR-139-5p, miR-205-5p, miR-221-3p, miR-375-3p, miR-382-5p, and miR-384-5p, contribute to aberrant Runx expression in prostate tumors. Our studies reveal a Runx/miRNA interaction axis centered on PTEN-PI3K-AKT signaling. This regulatory network translates to mechanistic understanding of prostate tumorigenesis that can be developed for diagnosis and directed therapy.

Recommended Citation

Farina, Nicholas H; Zingiryan, Areg; Akech, Jacqueline A; Callahan, Cody J; Lu, Huimin; Stein, Janet L; Languino, Lucia R; Stein, Gary S; and Lian, Jane B, "A microRNA/Runx1/Runx2 network regulates prostate tumor progression from onset to adenocarcinoma in TRAMP mice." (2016). Department of Cancer Biology Faculty Papers. Paper 104.
https://jdc.jefferson.edu/cbfp/104

Creative Commons License

This work is licensed under a Creative Commons Attribution 3.0 License.

PubMed ID

27634876