4.4 Article

MicroRNA-148a promotes apoptosis and suppresses growth of breast cancer cells by targeting B-cell lymphoma 2

Journal

ANTI-CANCER DRUGS
Volume 28, Issue 6, Pages 588-595

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CAD.0000000000000498

Keywords

apoptosis; B-cell lymphoma 2; breast cancer; microRNAs; proliferation

Funding

  1. National Science Foundation Committee (NSFC) of China [81271582, 81471678]

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MicroRNAs (miRNAs) contribute toward tumorigenesis through the modulation of tumor-related genes. MiR-148a has been characterized as a tumor-suppressing miRNA and its downregulation has been reported in tumors of a variety of cancers. However, the functional role of miR-148a in breast cancer is not yet fully understood. Using both in-vitro and in-vivo models, we confirmed that miR-148a acts to inhibit the proliferation of breast cancer cells. Through the use of bioinformatic approaches in miRNA target prediction, we determined that B-cell lymphoma 2 (BCL-2) is a likely target of miR-148a. The overexpression and tumorigenic effects of BCL-2 have already been confirmed in cancerous tumors of the breast. A dual-luciferase assay was performed to confirm that miR-148a targets the 3'-untranslated region of BCL-2. In this study, we first characterized the downregulation of miR-148a in breast cancer tissues. We then found that restoring expression of miR-148a suppressed the expression of BCL-2 at the level of both mRNA and protein. Upregulation of miR-148a caused a subsequent reduction of proliferation and an increase in apoptosis. In conclusion, we have confirmed the role of miR-148a as a pivotal regulator in breast cancer through its targeting of BCL-2. This evidence strongly suggests that miR-148a could prove to be a novel therapeutic target in breast cancer. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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