Abstract

BackgroundMicroRNAs (miRNAs) play an important role in the regulation of cell growth, differentiation, apoptosis, and carcinogenesis. Detection of their expression may lead to identifying novel markers for breast cancer.MethodsWe profiled miRNA expression in three breast cancer cell lines (MCF-7, MDA-MB-231, and MDA-MB-468) and then focused on one miRNA, miR-339-5p, for its role in regulation of tumor cell growth, migration, and invasion and target gene expression. We then analyzed miR-339-5p expression in benign and cancerous breast tissue specimens.ResultsA number of miRNAs were differentially expressed in these cancer cell lines. Real-time PCR indicated that miR-339-5p expression was downregulated in the aggressive cell lines MDA-MB-468 and MDA-MB-231 and in breast cancer tissues compared with benign tissues. Transfection of miR-339-5p oligonucleotides reduced cancer cell growth only slightly but significantly decreased tumor cell migration and invasion capacity compared with controls. Real-time PCR analysis showed that BCL-6, a potential target gene of miR-339-5p, was downregulated in MDA-MB-231 cells by miR-339-5p transfection. Furthermore, the reduced miR-339-5p expression was associated with an increase in metastasis to lymph nodes and with high clinical stages. Kaplan-Meier analyses found that the patients with miR-339-5p expression had better overall and relapse-free survivals compared with those without miR-339-5p expression. Cox proportional hazards analyses showed that miR-339-5p expression was an independent prognostic factor for breast cancer patients.ConclusionsMiR-339-5p may play an important role in breast cancer progression, suggesting that miR-339-5p should be further evaluated as a biomarker for predicting the survival of breast cancer patients.

Highlights

  • MicroRNAs play an important role in the regulation of cell growth, differentiation, apoptosis, and carcinogenesis

  • We found that levels of miR-339-5p expression in breast cancer with lymph node metastasis were significantly lower than levels for breast cancer without lymph node metastasis or for benign disease (P < 0.01, Fig. 1B)

  • We found that knockdown of miR-339-5p expression in MCF-7 cells using miR-339-5p antisense oligonucleotides (ASO) did not significantly reduce the cell viability (Fig. 2A), and expression of miR-339-5p in MDA-MB-231 cells using miR-339-5p mimic oligonucleotides did not induce tumor cell growth

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Summary

Introduction

MicroRNAs (miRNAs) play an important role in the regulation of cell growth, differentiation, apoptosis, and carcinogenesis. Detection of their expression may lead to identifying novel markers for breast cancer. MiR-21, miR-10b, and miR-335 have been shown to be involved in the formation and progression of breast cancer by targeting certain oncogenes or tumor suppressors [5,6,7]. A number of studies have found that miRNAs play an important role in the regulation of cell growth, differentiation, apoptosis, and carcinogenesis [8,9,10,11,12,13]

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