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miR‐199a‐5p regulates β1 integrin through Ets‐1 to suppress invasion in breast cancer
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miR‐199a‐5p regulates β1 integrin through Ets‐1 to suppress invasion in breast cancer
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Journal Article
miR‐199a‐5p regulates β1 integrin through Ets‐1 to suppress invasion in breast cancer
2016
Overview
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.
Our results provide insight into the regulation of β1 integrin through miR‐199a‐5p‐mediated Ets‐1 silence and help in designing new therapeutic strategies to inhibit signal pathways induced by miR‐199a‐5p in breast cancer invasion.
Publisher
John Wiley & Sons, Inc,John Wiley and Sons Inc
Subject
/ 3' Untranslated Regions - genetics
/ Breast Neoplasms - pathology
/ Ets‐1
/ Female
/ Focal Adhesion Kinase 1 - metabolism
/ Humans
/ integrin
/ Integrin beta1 - biosynthesis
/ invasion
/ Kinases
/ Ligands
/ mRNA
/ Neoplasm Invasiveness - genetics
/ Original
/ Patients
/ Phosphorylation - drug effects
/ Proteins
/ Proto-Oncogene Protein c-ets-1 - deficiency
/ Proto-Oncogene Protein c-ets-1 - genetics
/ Proto-Oncogene Protein c-ets-1 - metabolism
/ Proto-Oncogene Proteins c-akt - antagonists & inhibitors
/ Proto-Oncogene Proteins c-akt - metabolism
/ Signal Transduction - genetics
/ siRNA
/ src-Family Kinases - antagonists & inhibitors
/ src-Family Kinases - metabolism
/ TOR Serine-Threonine Kinases - metabolism
/ Transcription, Genetic - genetics
/ Tumors
