miR-199a-5p regulates β1 integrin through Ets-1 to suppress invasion in breast cancer.
Increasing evidence has revealed that miR-199a-5p is actively involved in tumor invasion and metastasis as well as in the decline of breast cancer tissues. In this research, overexpression of miR-199a-5p weakened motility and invasion of breast cancer cells MCF-7 and MDA-MB-231. Upregulation of Ets-1 increased breast cancer cell invasion, but the mechanism by which miR-199a-5p modulates activation of Ets-1 in breast cancer was not clarified. We investigated the relationship between miR-199a-5p and Ets-1 on the basis of 158 primary breast cancer case specimens, and the results showed that Ets-1 expression was inversely correlated with endogenous miR-199a-5p. Overexpression of miR-199a-5p reduced the mRNA and protein levels of Ets-1 in MCF-7 and MDA-MB-231 cells, whereas anti-miR-199a-5p elevated Ets-1. siRNA-mediated Ets-1 knockdown phenocopied the inhibition invasion of miR-199a-5p in vitro. Moreover, luciferase reporter assay revealed that miR-199a-5p directly targeted 3'-UTR of Ets-1 mRNA. This research revealed that miR-199a-5p could descend the levels of β1 integrin by targeting 3'-UTR of Ets-1 to alleviate the invasion of breast cancer via FAK/Src/Akt/mTOR signaling pathway. Our results provide insight into the regulation of β1 integrin through miR-199a-5p-mediated Ets-1 silence and will help in designing new therapeutic strategies to inhibit signal pathways induced by miR-199a-5p in breast cancer invasion.
Department of Pathology, Weifang Medical University, Weifang, Shandong Province, China.
Wentong
W
Li
Second Department of Oncology, People's Hospital of Shouguang City, Shouguang, Shandong Province, China.
Hui
H
Wang
Department of Molecular Genetics, Weifang Medical University, Weifang, Shandong Province, China.
Jinbao
J
Zhang
Department of Pathology, Weifang Medical University, Weifang, Shandong Province, China.
Limin
L
Zhai
Department of Pathology, People's Hospital of Shouguang City, Shouguang, Shandong Province, China.
Weijuan
W
Chen
Department of Biology, Weifang Medical University, Weifang, Shandong Province, China.
Chunling
C
Zhao
D020413:3' Untranslated Regions / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000096:biosynthesis / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics*; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D050784:Proto-Oncogene Protein c-ets-1 / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D020413:3' Untranslated Regions; C494041:ETS1 protein, human; D019012:Integrin beta1; D035683:MicroRNAs; D050784:Proto-Oncogene Protein c-ets-1; C531408:mirn199 microRNA, human; C546842:MTOR protein, human; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
Breast cancer; Ets-1; integrin; invasion; miRNA-199a