miR-19 targeting of PTEN mediates butyl benzyl phthalate-induced proliferation in both ER(+) and ER(-) breast cancer cells.

Abstract

Breast cancer is the most common cancer among women worldwide. Butyl benzyl phthalate (BBP) is ubiquitous in human's environment, and is strongly linked to breast cancer development. microRNA (miRNA) is an important regulator of target genes. So far, no studies have been reported yet to reveal the action of miRNAs in BBP-mediated breast cancer cell proliferation. In this study, we showed that BBP induced proliferation of both ER(+) MCF-7 and ER(-) MDA-MB-231 breast cancer cells, proved by increased cell viability, transition of cell cycle from G1 to S phase, upregulation of proliferating cell nuclear antigen (PCNA) and Cyclin D1, and downregulation of p21. Meanwhile, the expression of oncogenic miR-19a/b and PTEN/AKT/p21 axis was also modulated by BBP. Furthermore, for the first time we revealed that miR-19 played crucial role in the promoting effect of BBP on breast cancer cells through targeting PTEN 3'UTR. Findings from this study could provide an important new perspective on the molecular mechanisms through which BBP exerts its promoting effect on breast cancer as well as its target intervention.

• Authors: Jieshu Wu, Ye Jiang, Wanshuang Cao, Xiaoting Li, Chunfeng Xie, Shanshan Geng, Mingming Zhu, Zhaofeng Liang, Jianyun Zhu, Weiwei Zhu, Rui Wu, Xiao Ma, Cong Huang, Xue Yang, Shijia Wang, Caiyun Zhong
• Journal: Toxicology letters (Toxicol Lett) Vol. 295 Pg. 124-133 (Oct 01 2018) ISSN: 1879-3169 [Electronic] Netherlands
• PMID: 29864457 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• 3' Untranslated Regions
• CCND1 protein, human
• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• MIRN19 microRNA, human
• MicroRNAs
• Phthalic Acids
• Plasticizers
• Proliferating Cell Nuclear Antigen
• Receptors, Estrogen
• Cyclin D1
• Proto-Oncogene Proteins c-akt
• PTEN Phosphohydrolase
• PTEN protein, human
• butylbenzyl phthalate

Topics

• 3' Untranslated Regions
• Binding Sites
• Breast Neoplasms (chemically induced, genetics, metabolism, pathology)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cell Transformation, Neoplastic (chemically induced, genetics, metabolism, pathology)
• Cyclin D1 (metabolism)
• Cyclin-Dependent Kinase Inhibitor p21 (metabolism)
• Dose-Response Relationship, Drug
• Female
• G1 Phase Cell Cycle Checkpoints (drug effects)
• Gene Expression Regulation, Enzymologic
• Gene Expression Regulation, Neoplastic
• Humans
• MCF-7 Cells
• MicroRNAs (genetics, metabolism)
• PTEN Phosphohydrolase (genetics, metabolism)
• Phthalic Acids (toxicity)
• Plasticizers (toxicity)
• Proliferating Cell Nuclear Antigen (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Receptors, Estrogen (metabolism)
• Signal Transduction (drug effects)
• Time Factors