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Molecules 2014, 19(6), 7122-7137; https://doi.org/10.3390/molecules19067122

miR-221/222 Promotes S-Phase Entry and Cellular Migration in Control of Basal-Like Breast Cancer

1
Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China
2
Lanzhou University School of Pharmacy, the First Affiliated Hospital of Lanzhou University, Lanzhou, Gansu 730000, China
3
Department of Anatomy, Histology and Embryology, Shanghai Medical College, Fudan University, Shanghai 200120, China
4
Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, China
5
Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
These authors contribute equally to this work.
*
Author to whom correspondence should be addressed.
Received: 2 April 2014 / Revised: 22 May 2014 / Accepted: 26 May 2014 / Published: 30 May 2014
(This article belongs to the Special Issue miRNAs as Probes to Monitor Cancer and Neurodegenerative Disorders)
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Abstract

The miR-221/222 cluster has been demonstrated to function as oncomiR in human cancers. miR-221/222 promotes epithelial-to-mesenchymal transition (EMT) and confers tamoxifen resistance in breast cancer. However, the effects and mechanisms by which miR-221/222 regulates breast cancer aggressiveness remain unclear. Here we detected a much higher expression of miR-221/222 in highly invasive basal-like breast cancer (BLBC) cells than that in non-invasive luminal cells. A microRNA dataset from breast cancer patients indicated an elevated expression of miR-221/222 in BLBC subtype. S-phase entry of the cell cycle was associated with the induction of miR-221/222 expression. miRNA inhibitors specially targeting miR-221 or miR-222 both significantly suppressed cellular migration, invasion and G1/S transition of the cell cycle in BLBC cell types. Proteomic analysis demonstrated the down-regulation of two tumor suppressor genes, suppressor of cytokine signaling 1 (SOCS1) and cyclin-dependent kinase inhibit 1B (CDKN1B), by miR-221/222. This is the first report to reveal miR-221/222 regulation of G1/S transition of the cell cycle. These findings demonstrate that miR-221/222 contribute to the aggressiveness in control of BLBC. View Full-Text
Keywords: miR-221; miR-222; basal-like breast cancer; migration; cell cycle miR-221; miR-222; basal-like breast cancer; migration; cell cycle
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Li, Y.; Liang, C.; Ma, H.; Zhao, Q.; Lu, Y.; Xiang, Z.; Li, L.; Qin, J.; Chen, Y.; Cho, W.C.; Pestell, R.G.; Liang, L.; Yu, Z. miR-221/222 Promotes S-Phase Entry and Cellular Migration in Control of Basal-Like Breast Cancer. Molecules 2014, 19, 7122-7137.

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