MiR-221/222 promote cancer stem-like cell properties and tumor growth of breast cancer via targeting PTEN and sustained Akt/NF-κB/COX-2 activation. (1st November 2017)

• Record Type: Journal Article
• Authors: Li, Bailong; Lu, Ying; Yu, Lihui; Han, Xiaocui; Wang, Honghai; Mao, Jun; Shen, Jie; Wang, Bo; Tang, Jianwu; Li, Chunyan; Song, Bo
• Is Part Of: Chemico-biological interactions. Volume 277(2017)
• Page Start: 33
• Page End: 42
• Publication Date: 2017-11-01
• Subjects: MicroRNA-221/222 -- PTEN/Akt pathway -- NF-κB -- Cyclooxygenase-2 -- Cancer stem cell -- Breast cancer; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2017.08.014
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: MicroRNAs (miRNAs) play an important role in regulating cancer stem cell (CSC). Previous studies have shown that microRNA-221/222 (miR-221/222) cluster are involved in the propagation of breast cancer stem cell (BCSC), however, the underlying molecular mechanisms are still not fully understood. In this study, we found that miR-221/222 were overexpressed in highly aggressive breast cancer MDA-MB-231 cells, that are enriched in markers for epithelial-mesenchymal transition (EMT) and BCSCs, than in MCF-7 cells. Phosphatase and tensin homolog (PTEN) was confirmed to be the target of miR-221/222 in breast cancer cells. MiR-221/222 enhanced breast cancer cell growth, migration and invasion by downregulating PTEN. Importantly, both ectopic expression of miR-221/222 and PTEN knockdown increased the mammosphere formation capacity and the expression of the stemness marker ALDH1. MiR-221/222 lentivirus vector infected MCF-7 cells produced larger subcutaneous tumors, while shRNA vector of PTEN showed similar trend. Along with the downregulation of PTEN caused by miR-221/222 in the breast cancer cells and the xenograft tumor tissues, Akt phosphorylation (p-Akt), NF-κB p65 and phosphorylated p65 (p-p65), and cyclooxygenase-2 (COX-2) were all overexpressed compared to the negative control. Taken together, our findings indicate that miR-221/222 play a critical role in the propagation of BCSCs and tumor growth possibly through targeting PTEN, which in turn activating the Akt/NF-κB/COX-2 pathway. MiR-221/222 might represent the potential target of breast cancer therapy. Highlights: In vitro and in vivo experiments show that miR-221/222 enhance self-renewal of BCSC. Propagation of BCSC by miR-221/222 is possibly through PTEN/Akt/NF-κB/COX-2 pathway. Therapeutics against miR-221/222 might represent a novel strategy for breast cancer.