MiR-646 inhibited cell proliferation and EMT-induced metastasis by targeting FOXK1 in gastric cancer

• Published in: British journal of cancer 2017-08, Vol.117 (4), p.525-534
• Main Authors: Zhang, P, Tang, W M, Zhang, H, Li, Y Q, Peng, Y, Wang, J, Liu, G N, Huang, X T, Zhao, J J, Li, G, Li, A M, Bai, Y, Chen, Y, Ren, Y X, Li, G X, Wang, Y D, Liu, S D, Wang, J D
• Format: Article
• Language: English
• Subjects: 631/337/384/331; 631/80/84/2176; 692/4028/67/1504/1829; 692/4028/67/322; AKT protein; Animals; Assaying; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell growth; Cell Line, Tumor; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Down-Regulation; Drug Resistance; Epidemiology; Epithelial-Mesenchymal Transition - drug effects; Female; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Gastric cancer; Humans; Lymphatic Metastasis; Mesenchyme; Metastases; Metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs - antagonists & inhibitors; MicroRNAs - genetics; MicroRNAs - metabolism; MicroRNAs - pharmacology; Migration; miRNA; Molecular Diagnostics; Molecular Medicine; Molecular modelling; Neoplasm Invasiveness; Neoplasm Staging; Neoplasm Transplantation; Oncology; Phenotype; Polymerase chain reaction; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Tissues; TOR protein; TOR Serine-Threonine Kinases - metabolism; Transfection; Transforming Growth Factor beta1 - pharmacology; Transforming growth factor-b1; Tumor Burden; Tumor Stem Cell Assay; Tumors; Western blotting
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2017.181

Background: MiR-646 has been reported to be aberrantly expressed in human cancers. However, the underlying molecular mechanisms of action of miR-646 in gastric cancer (GC) have not yet been investigated. Methods: In vitro function of miR-646 in GC was evaluated using EdU assay, plate colony formation assay, and matrigel invasion assay. Real-time PCR or western blotting was performed to detect miR-646 and FOXK1 expressions. In vivo tumour growth and metastasis were conducted in nude mice. Results: MiR-646 expression was downregulated in GC tissues compared with adjacent normal tissues. Low miR-646 expression is associated with malignant progression. Transient transfection of GC cells with miR-646 inhibited their growth and migration. Moreover, miR-646 influenced the expression of epithelial–mesenchymal transition (EMT)-associated proteins. TGF- β 1 treatment significantly suppressed the expression of miR-646 and overexpression of this microRNA counteracted the influence of the TGF- β 1-induced EMT phenotype. In terms of the underlying mechanism, miR-646 directly targeted FOXK1. In vivo , it inhibited the FOXK1-mediated proliferation and EMT-induced metastasis. Consistently, inverse correlations were also observed between the expression of miR-646 and FOXK1 in human GC tissue samples. Furthermore, miR-646 regulated Akt/mTOR signalling after FOXK1. Conclusions: miR-646 inhibited GC cell proliferation and the EMT progression in GC cells by targeting FOXK1.