Abstract
MicroRNA-326 (miR-326) was reported to be dysregulated and involved in the progression of multiple cancers. However, the clinical significance, biological role and underlying mechanism of miR-326 in the carcinogenesis of breast cancer are still unclear. In the present study, we showed that miR-326 was down-regulated in human breast cancer tissues and cell lines. Our results also revealed that miR-326 overexpression significantly suppressed breast cancer cell proliferation, migration and invasion, and induced cell cycle arrest at G1/G0 phase. Furthermore, Sex determining region Y-box (SOX) protein 12 (SOX12), a known oncogene, was identified as a direct target of miR-326 by luciferase reporter assay. Moreover, miR-326 expression was inversely correlated with SOX12 mRNA expression levels in human breast cancer specimens. Overexpression of SOX12 partially rescued the inhibitory effect on cell proliferation, migration and invasion in breast cancer cells caused by miR-326 overexpression. These findings suggested that miR-326 might play a suppressive role in breast cancer, at least in part, by targeting SOX12, rendering miR-326 a promising therapeutic target for breast cancer.
Highlights
Breast cancer is one of the most common malignant malignancies in women worldwide [1]
The major finding of the current study was that miR-326 inhibited proliferation and invasion of breast cancer cells through targeting Sex determining region Y-box protein 12 (SOX12), revealing a novel epigenetic mechanism of how miR-326 played a tumor suppressive role in breast cancer
We identified for the first time that the tumor suppressor role of miR-326 in breast cancer by a series of experiments
Summary
Breast cancer is one of the most common malignant malignancies in women worldwide [1]. Despite considerable improvements in therapeutic strategies for breast cancer including multi-agent chemotherapy, surgery and radiotherapy, the 5-year survival rate of breast cancer has not improved significantly due to tumor metastasis and recurrence [2,3]. It is urgently needed to understand the molecular mechanisms involved in development and progression of breast cancer for identifying novel and effective diagnosis markers and therapeutic targets. Growing evidence has demonstrated the vital function of miRNAs in multiple biological processes, including proliferation, apoptosis, cycle arrest, differentiation, metabolism and metastasis [5]. Dysregulation of miRNAs have been revealed to be involved in initiation and development of various cancers [6,7]. Number of miRNAs was identified to be involved in progression of breast cancer, suggesting that miRNAs can serve as diagnosis marker and therapy agent [8–10]
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