MicroRNA-449b-5p suppresses the growth and invasion of breast cancer cells via inhibiting CREPT-mediated Wnt/β-catenin signaling.

Abstract

Accumulating evidence has suggested that microRNA-449b-5p (miR-449b-5p) plays an important role in the development and progression of multiple cancers. However, little is known about the role of miR-449b-5p in breast cancer. In this study, we aimed to investigate the expression level, biological function and underlying mechanism of miR-449b-5p in breast cancer. Our results showed that miR-449b-5p expression was frequently down-regulated in breast cancer cell lines and tissues. The overexpression of miR-449b-5p significantly inhibited growth and invasion, and induced the cell cycle arrest of breast cancer cells. In contrast, the inhibition of miR-449b-5p showed the opposite effect. Interestingly, bioinformatic analysis predicted that cell cycle-related and expression-elevated protein in tumor (CREPT), an important oncogene in breast cancer, was a potential target gene of miR-449b-5p. The overexpression of miR-449b-5p decreased CREPT expression while miR-449b-5p inhibition promoted CREPT expression in breast cancer cells. Restoration of CREPT expression in miR-449b-5p mimics transfected cells partially reversed the suppressive effect of miR-449b-5p on breast cancer cell growth and invasion. Notably, our results showed that miR-449b-5p overexpression decreased the expression of β-catenin and suppressed the activation of Wnt/β-catenin/TCF-4 signaling via targeting CREPT. In addition, blocking Wnt/β-catenin partially reversed the promotion effect of miR-449b-5p inhibition on breast cancer cell growth and invasion. Overall, these results reveal a tumor suppressive role of miR-449b-5p that restricts the growth and invasion of breast cancer cells through targeting CREPT and inhibiting CREPT-mediated activation of Wnt/β-catenin signaling. Our study suggests that the miR-449b-5p/CREPT/Wnt/β-catenin axis may play an important role in the pathogenesis of breast cancer and miR-449-5p may serve as a potential therapeutic target for breast cancer.

• Authors: Jue Jiang, Xiaoyun Yang, Xin He, Wenqi Ma, Juan Wang, Qi Zhou, Miao Li, Shanshan Yu
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 302 Pg. 74-82 (Apr 01 2019) ISSN: 1872-7786 [Electronic] Ireland
• PMID: 30738779 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• 3' Untranslated Regions
• Antagomirs
• Cell Cycle Proteins
• MIRN449 microRNA, human
• MicroRNAs
• Neoplasm Proteins
• RPRD1B protein, human
• Transcription Factor 4
• Wnt Proteins
• beta Catenin

Topics

• 3' Untranslated Regions
• Antagomirs (metabolism)
• Binding Sites
• Breast Neoplasms (genetics, metabolism, pathology)
• Cell Cycle Proteins (chemistry, genetics, metabolism)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Female
• Humans
• MCF-7 Cells
• MicroRNAs (antagonists & inhibitors, genetics, metabolism)
• Neoplasm Proteins (chemistry, genetics, metabolism)
• Transcription Factor 4 (metabolism)
• Wnt Proteins (metabolism)
• Wnt Signaling Pathway
• beta Catenin (metabolism)