miR-21: A gene of dual regulation in breast cancer

Zhang,Chunfu; Liu,Kui; Li,Tao; Fang,Jie; Ding,Yanling; Sun,Lingxian; Tu,Tao; Jiang,Xinyi; Du,Shanmei; Hu,Jiabo; Zhu,Wei; Chen,Huabiao; Sun,Xiaochun

doi:10.3892/ijo.2015.3232

miR-21: A gene of dual regulation in breast cancer

Authors:
- Chunfu Zhang
- Kui Liu
- Tao Li
- Jie Fang
- Yanling Ding
- Lingxian Sun
- Tao Tu
- Xinyi Jiang
- Shanmei Du
- Jiabo Hu
- Wei Zhu
- Huabiao Chen
- Xiaochun Sun
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Affiliations: The Second People's Hospital of Kunshan, Kunshan, Jiangsu 215300, P.R. China, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China, Zibo Vocational Institute, Zibo, Shandong 255314, P.R. China
Published online on: November 5, 2015 https://doi.org/10.3892/ijo.2015.3232
Pages: 161-172

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Abstract

Breast cancer is characterized by an elevated capacity for tumor invasion and lymph node metastasis, but the cause remains to be determined. Recent studies suggest that microRNAs (miRNAs) can regulate the evolution of malignant behavior by regulating multiple target genes. A key oncomir in carcinogenesis is miR-21, which is consistently upregulated in a wide range of cancers. However, few functional studies are available for miR-21, and few targets have been identified. In this study, we explored the role of miR-21 in human breast cancer cells and searched for miR-21 targets.Total RNA from breast cancer tissue and corresponding adjacent normal tissue was extracted and used to detect miR-21 expression by quantificational real-time polymerase chain reaction (qRT-PCR), followed by analysis of the correlation between gonad hormone indices in peripheral blood and miR-21 expression in cancerous tissues from the same patients. Cell proliferation, colony formation, migration and invasion were then examined to determine the role of miR-21 in regulating breast cancer cells. Finally, western blotting was performed to determine if miR-21 regulated expression of signal transducers and activators of transcription 3 (STAT3), and assays of cell proliferation, colony formation, migration and invasion were performed to examine the role of STAT3 in regulation of breast cancer cells. We found that expression of miR-21 increased from normal through benign to cancerous breast tissues. Enhanced miR-21 expression was associated with serum levels of follicle-stimulating hormone, estradiol, β-human chorionic gonadotropin, testosterone and prolactin in patients with breast cancer. Furthermore, cell proliferation, colony formation, migration and invasion were increased after overexpression of miR-21 in breast cancer cells and reduced by miR-21 suppression. In addition, we identified a putative miR-21 binding site in the 3'-untranslated region of the STAT3 gene using an online bioinformatical tool. We found that protein expression of STAT3 was significantly downregulated when breast cancer cells were transfected with miR-21 mimics, and was significantly upregulated in breast cancer cells transfected with a miR-21 inhibitor. Finally, we found that cell proliferation, colony formation, migration and invasion were decreased by treatment with 2.5 nM of Stattic, an inhibitor of STAT3 activation. Our data suggest that miR-21 expression is increased in breast cancer and plays an important role as a tumor gene by targeting STAT3, which may act as a double-response controller in breast cancer.

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