MicroRNA-543 suppresses endometrial cancer oncogenicity via targeting FAK and TWIST1 expression.

INTRODUCTION: Focal adhesion kinase (FAK) is a critical mediator of extracellular matrix signaling, cell survival, proliferation and motility. Twist homolog 1 (TWIST1) is a transcription factor and serves as a powerful oncogene. Increased FAK and TWIST1 expression are observed in a variety of solid human tumors and correlate with metastasis and poor survival.

MATERIALS AND METHODS: Here, we identify miR-543 as a direct regulator of FAK and TWIST1 expression in endometrial cancer.

RESULTS: Forced expression of miR-543 in endometrial cancer cell lines decreases both endogenous FAK and TWIST1 mRNA and protein levels. Forced expression of miR-543 in aggressive endometrial cancer cell lines also impairs tumor cell monolayer proliferation, anchorage-independent growth, migration and invasion. Endogenous miR-543 expression is decreased in malignant versus normal endometrium tissue and the levels of miR-543 inversely correlate with mRNA levels of FAK and TWIST1.

CONCLUSIONS: miR-543 expression is decreased in endometrial cancer and serves as a tumor suppressor by targeting FAK and TWIST1 expression.