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


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.
Department of Gynecology and Obstetrics, The Military General Hospital of Beijing PLA, Beijing, 100700, China.
Li
L
Bing
Chen
C
Hong
Shang
S
Li-Xin
Gao
G
Wei
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D015153:Blotting, Western; D002277:Carcinoma / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology*; D004717:Endometrium / Q000378:metabolism; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D051879:Twist-Related Protein 1 / Q000235:genetics* / Q000378:metabolism
C577592:MIRN543 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D012333:RNA, Messenger; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D051416:Focal Adhesion Protein-Tyrosine Kinases