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.
Highlights
Breast cancer is the most common non-cutaneous cancer in women
MiR-221/222 is a miRNA cluster located on chromosome X (Figure 1A) where the genome abnormality occurs often contributing to the pathogenesis of basal-like human breast cancer [9,18]
In order to determine the effects of miR-221/222 on cellular migration and invasion in breast cancer, miR-221/222 expression was examined in highly invasive breast cancer cell lines Hs578t, MDA-MB-231 and SUM159, and in non-invasive breast cancer cell lines MCF-7, MDA-MB-453 and T-47D as well
Summary
Breast cancer is the most common non-cutaneous cancer in women. the traditional treatment therapies and surgery may decrease tumor size, reduce tumor growth rate and prolong patient survival, the 5-year survival in metastatic breast cancer is ~27% compared to 98% for localized breast cancer [1]. MiR-21, the most abundant miRNA in human breast cancer MCF-7 cells, enhances MCF-7 cell proliferation in vitro and promotes MCF-7 derived tumorigenesis in vivo by inhibiting the expression of a subset of tumor suppressor genes including several p53-regulated genes [11]. MiR-27 increases the human breast cancer MDA-MB-231 cell proliferation through regulating the cell cycle. MiRNA let-7 inhibits self-renewal and induces differentiation of human breast cancer stem cells (CSC). MiR-221/222 is a miRNA cluster located on chromosome X (Figure 1A) where the genome abnormality occurs often contributing to the pathogenesis of basal-like human breast cancer [9,18]. The mechanism by which the miR-221/222 cluster affects cellular proliferation, cell cycle, cellular migration and invasion in BLBC remains unclear. We identified a novel target gene of miR-221/222, suppressor of cytokine signaling 1 (SOCS1), in human breast cancer
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
