RRC ID 45048
Author Mitamura T, Watari H, Wang L, Kanno H, Kitagawa M, Hassan MK, Kimura T, Tanino M, Nishihara H, Tanaka S, Sakuragi N.
Title microRNA 31 functions as an endometrial cancer oncogene by suppressing Hippo tumor suppressor pathway.
Journal Mol. Cancer
Abstract BACKGROUND:We aimed to investigate whether MIR31 is an oncogene in human endometrial cancer and identify the target molecules associated with the malignant phenotype.
METHODS:We investigated the growth potentials of MIR31-overexpressing HEC-50B cells in vitro and in vivo. In order to identify the target molecule of MIR31, a luciferase reporter assay was performed, and the corresponding downstream signaling pathway was examined using immunohistochemistry of human endometrial cancer tissues. We also investigated the MIR31 expression in 34 patients according to the postoperative risk of recurrence.
RESULTS:The overexpression of MIR31 significantly promoted anchorage-independent growth in vitro and significantly increased the tumor forming potential in vivo. MIR31 significantly suppressed the luciferase activity of mRNA combined with the LATS2 3'-UTR and consequently promoted the translocation of YAP1, a key molecule in the Hippo pathway, into the nucleus. Meanwhile, the nuclear localization of YAP1 increased the transcription of CCND1. Furthermore, the expression levels of MIR31 were significantly increased (10.7-fold) in the patients (n = 27) with a high risk of recurrence compared to that observed in the low-risk patients (n = 7), and this higher expression correlated with a poor survival.
CONCLUSIONS:MIR31 functions as an oncogene in endometrial cancer by repressing the Hippo pathway. MIR31 is a potential new molecular marker for predicting the risk of recurrence and prognosis of endometrial cancer.
Volume 13
Pages 97
Published 2014-4-29
DOI 10.1186/1476-4598-13-97
PII 1476-4598-13-97
PMID 24779718
PMC PMC4067122
MeSH Adaptor Proteins, Signal Transducing / biosynthesis* Adaptor Proteins, Signal Transducing / genetics Adult Aged Apoptosis Cell Line, Tumor Cyclin D1 / biosynthesis* Cyclin D1 / genetics Cyclin D1 / metabolism Endometrial Neoplasms / genetics* Endometrial Neoplasms / pathology Female Gene Expression Regulation, Neoplastic Genes, Tumor Suppressor Humans MicroRNAs / genetics* Middle Aged Neoplasm Recurrence, Local Phosphoproteins / biosynthesis* Phosphoproteins / genetics Protein-Serine-Threonine Kinases / biosynthesis* Protein-Serine-Threonine Kinases / genetics Signal Transduction / genetics Tumor Suppressor Proteins / biosynthesis* Tumor Suppressor Proteins / genetics
IF 10.679
Times Cited 14
Human and Animal Cells