Lipid raft-mediated miR-3908 inhibition of migration of breast cancer cell line MCF-7 by regulating the interactions between AdipoR1 and Flotillin-1.
BACKGROUND
The mechanisms of lipid raft regulation by microRNAs in breast cancer are not fully understood. This work focused on the evaluation and identification of miR-3908, which may be a potential biomarker related to the migration of breast cancer cells, and elucidates lipid-raft-regulating cell migration in breast cancer.


METHODS
To confirm the prediction that miR-3908 is matched with AdipoR1, we used 3'-UTR luciferase activity of AdipoR1 to assess this. Then, human breast cancer cell line MCF-7 was cultured in the absence or presence of the mimics or inhibitors of miR-3908, after which the biological functions of MCF-7 cells were analyzed. The protein expression of AdipoR1, AMPK, and SIRT-1 were examined. The interaction between AdipoR1 and Flotillin-1, or its effects on lipid rafts on regulating cell migration of MCF-7, was also investigated.


RESULTS
AdipoR1 is a direct target of miR-3908. miR-3908 suppresses the expression of AdipoR1 and its downstream pathway genes, including AMPK, p-AMPK, and SIRT-1. miR-3908 enhances the process of breast cancer cell clonogenicity. miR-3908 exerts its effects on the proliferation and migration of MCF-7 cells, which are mediated by lipid rafts regulating AdipoR1's ability to bind Flotillin-1.


CONCLUSIONS
miR-3908 is a crucial mediator of the migration process in breast cancer cells. Lipid rafts regulate the interactions between AdipoR1 and Flotillin-1 and then the migration process associated with miR-3908 in MCF-7 cells. Our findings suggest that targeting miR-3908 and the lipid raft, may be a promising strategy for the treatment and prevention of breast cancer.
Department of Obstetrics and Gynecology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, 100048, China.
Yuan
Y
Li
Department of Cardiac Surgery, Affiliated Hospital of Medical College of Yan'an University, Yan'an, Shanxi, 716000, China.
Fei
F
Shan
Department of Oncology, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China. dtzlzx@sina.com.
Jinglong
J
Chen
D020413:3' Untranslated Regions / Q000235:genetics*; D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D021962:Membrane Microdomains / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020413:3' Untranslated Regions; C475418:ADIPOR1 protein, human; D008565:Membrane Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D054419:Receptors, Adiponectin; C106354:flotillins
AdipoR1; Breast carcinoma; Flotillin-1; Lipid raft; MicroRNA; Migration