miR-661 expression in SNAI1-induced epithelial to mesenchymal transition contributes to breast cancer cell invasion by targeting Nectin-1 and StarD10 messengers

• Published in: Oncogene Vol. 29; no. 31; pp. 4436 - 4448
• Main Authors: Vetter, G, Saumet, A, Moes, M, Vallar, L, Le Béchec, A, Laurini, C, Sabbah, M, Arar, K, Theillet, C, Lecellier, C-H, Friederich, E
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.08.2010; Nature Publishing Group; Nature Publishing Group [1987-....]
• Subjects: 3' Untranslated regions; 631/337/384/331; 631/67/1347; 631/80/84/2176; 631/80/84/2336; Apoptosis; Biological and medical sciences; Breast cancer; Breast Neoplasms; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer; Cell adhesion; Cell adhesion & migration; Cell Adhesion Molecules; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell Biology; Cell Dedifferentiation; Cell Dedifferentiation - drug effects; Cell Dedifferentiation - genetics; Cell Dedifferentiation - physiology; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Development and progression; Down-regulation; Epithelial Cells; Epithelial Cells - metabolism; Epithelial Cells - physiology; Female; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene Expression - physiology; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Neoplastic - drug effects; Gene Expression Regulation, Neoplastic - physiology; Genetic aspects; Gynecology. Andrology. Obstetrics; Human Genetics; Humans; Internal Medicine; Life Sciences; Mammary gland diseases; Medical sciences; Medicine; Medicine & Public Health; Mesenchymal Stem Cells; Mesenchymal Stromal Cells - metabolism; Mesenchymal Stromal Cells - physiology; Mesenchyme; Messenger RNA; Metastases; Metastasis; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; MicroRNAs - physiology; miRNA; Molecular and cellular biology; Nectin; Nectins; Neoplasm Invasiveness; Oligonucleotide Array Sequence Analysis; Oncology; original-article; Phosphoproteins; Phosphoproteins - genetics; Phosphoproteins - metabolism; Physiological aspects; Proteins; Risk factors; RNA, Messenger; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Small Interfering; RNA, Small Interfering - pharmacology; Snail Family Transcription Factors; Snail protein; Transcription Factors; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription Factors - physiology; Transcriptomics; Tumor Cells, Cultured; Tumors; Validation Studies as Topic; France; Luxembourg; SNAI1; StarD10; breast cancer cell invasion; Nectin-1; EMT; miR-661; Breast disease; Targeting; Micro RNA; Breast cancer; Malignant tumor; Metastasis; Carcinogenesis; Mammary gland diseases; Gene silencing; Epithelium-to-mesenchymal transition; Cancer; EMT/miR-661/ SNAI1/StarD10/Nectin-1/breast cancer cell invasion
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2010.181

Epithelial to mesenchymal transition (EMT) is a key step toward metastasis. MCF7 breast cancer cells conditionally expressing the EMT master regulator SNAI1 were used to identify early expressed microRNAs (miRNAs) and their targets that may contribute to the EMT process. Potential targets of miRNAs were identified by matching lists of in silico predicted targets and of inversely expressed mRNAs. MiRNAs were ranked based on the number of predicted hits, highlighting miR-661, a miRNA with so far no reported role in EMT. MiR-661 was found required for efficient invasion of breast cancer cells by destabilizing two of its predicted mRNA targets, the cell–cell adhesion protein Nectin-1 and the lipid transferase StarD10, resulting, in turn, in the downregulation of epithelial markers. Reexpression of Nectin-1 or StarD10 lacking the 3′-untranslated region counteracted SNAI1-induced invasion. Importantly, analysis of public transcriptomic data from a cohort of 295 well-characterized breast tumor specimen revealed that expression of StarD10 is highly associated with markers of luminal subtypes whereas its loss negatively correlated with the EMT-related, basal-like subtype. Collectively, our non- a priori approach revealed a nonpredicted link between SNAI1-triggered EMT and the down-regulation of Nectin-1 and StarD10 through the up-regulation of miR-661, which may contribute to the invasion of breast cancer cells and poor disease outcome.