MicroRNA-99a inhibits tumor aggressive phenotypes through regulating HOXA1 in breast cancer cells
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Xiaolong Wang1, Yaming Li2, Wenwen Qi2, Ning Zhang1, Mingjuan Sun1, Qiang Huo1, Chang Cai1, Shangge Lv2, Qifeng Yang1,3
1Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, 250012, P.R. China
2School of Medicine, Shandong University, Jinan, Shandong, 250012, P.R. China
3Department of Pathology Tissue Bank, Qilu Hospital, Shandong University, Jinan, Shandong, 250012, P.R. China
Qifeng Yang, e-mail: [email protected]
Keywords: MiR-99a, HOXA1, breast cancer, proliferation, invasion
Received: April 16, 2015 Accepted: September 07, 2015 Published: September 19, 2015
MicroRNAs (miRNAs) are key regulators of tumor progression. Based on microarray data, we identified miR-99a as a potential tumor suppressor in breast cancer. Expression of miR-99a is frequently down-regulated in breast cancer tissues relative to normal breast tissues. Reduced miR-99a expression was highly associated with lymph node metastasis and shorter overall survival of patients with breast cancer. Gain- and loss-of-function studies revealed that, miR-99a significantly inhibits breast cancer cell proliferation, migration, and invasion. An integrated bioinformatics analysis identified HOXA1 mRNA as the direct functional target of miR-99a, and this regulation was confirmed by luciferase reporter assay. Furthermore, we showed for the first time that HOXA1 expression is elevated in breast cancer tissues. Knockdown of HOXA1 significantly inhibited breast cancer cell proliferation, migration and invasion, and restoration of HOXA1 partially rescued the inhibitory effect of miR-99a in breast cancer cells. Collectively, our data indicate that miR-99a plays a tumor-suppressor role in the development of breast cancer, and could serve as a potential therapeutic target for breast cancer treatment.
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