miR-221/222 promote cancer stem-like cell properties and tumor growth of breast cancer via targeting PTEN and sustained Akt/NF-Œ∫B/COX-2 activation
Authors: Chunyan Li
Honghai Wang
Bailong Li
Lihui Yu
Jie Shen
Xiaocui Han
Jianwu Tang
Bo Song
Ying Lu
Jun Mao
Bo Wang
Journal: Chemico-Biological Interactions (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Breast cancer; Cancer stem cell; Cyclooxygenase-2; MicroRNA-221/222; NF-Œ∫B
Affiliations: Department of Pathology and Forensics, Dalian Medical University, No.9 West Section, Lvshun South Road, Dalian 116044, China; Department of Clinical Medicine, Grade 2013, Dalian Medical University, No. 9 West Section, Lvshun South Road, Dalian 116044, China., Teaching Laboratory of Morphology, Dalian Medical University, No.9 West Section, Lvshun South Road, Dalian 116044, China., Department of Pathology and Forensics, Dalian Medical University, No.9 West Section, Lvshun South Road, Dalian 116044, China., Teaching Affairs Department, Dalian Medical University, No.9 West Section, Lvshun South Road, Dalian 116044, China., Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China. Electronic address: ., Department of Pathology and Forensics, Dalian Medical University, No.9 West Section, Lvshun South Road, Dalian 116044, China; Teaching Laboratory of Morphology, Dalian Medical University, No.9 West Section, Lvshun South Road, Dalian 116044, China. Electronic address: .

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-Œ∫B 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-Œ∫B/COX-2 pathway. MiR-221/222 might represent the potential target of breast cancer therapy. 

Retracted: No

PubPeer comments:
 In Figure 5A, flow cytometry data has been duplicated and presented as something else. Most of the flow cytometry data has very poor resolution and have a blurry appearance. Can the authors provide high resolution images?  ,