microRNA 31 functions as an endometrial cancer oncogene by suppressing Hippo tumor suppressor pathway

Abstract

BackgroundWe aimed to investigate whether MIR31 is an oncogene in human endometrial cancer and identify the target molecules associated with the malignant phenotype.MethodsWe 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.ResultsThe 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.ConclusionsMIR31 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.

Several microRNAs could predict survival in patients with hepatitis B-related liver cancer

“…This study by Creighton utilized only advanced stage cancers27; it did not also use early stage cancers. The expression levels of miR-31 were significantly increased in the patients with a high risk of recurrence compared to the low-risk patients, and higher expression of miR-31 correlated with a poor survival28. Our article supported Mitamura’s point of view28.…”

“…The expression levels of miR-31 were significantly increased in the patients with a high risk of recurrence compared to the low-risk patients, and higher expression of miR-31 correlated with a poor survival28. Our article supported Mitamura’s point of view28. Zhang reported miR-522 was upregulated in HCC cells; the overexpression miR522 could promote cell proliferation29.…”

LATS2 promoter hypermethylation and its effect on gene expression in human breast cancer

“…Such a reduction in the mRNA expression of LATS2 is likely to be induced by mechanisms other than promoter hypermethylation. Previously, several micoRNAs, including microRNA (miR)93 in breast cancer (13), miR25 in ovarian cancer (14) and miR31 in lung (15) and endometrial cancer (16), have been reported to directly target the LATS2 gene and reduce its anti-oncogenic effect. A previous study identified a LATS2 mutation, which can reduce the expression of the gene in lung cancer, however, such a mutation in breast cancer remains to be elucidated (2,3).…”

Hippo Signaling in the Liver Regulates Organ Size, Cell Fate, and Carcinogenesis

“…miR-9-3p has been reported to specifically target TAZ in hepatoma cell lines 95 , an activity which will need to be validated in vivo . Several other microRNAs to be considered with respect to the liver include LATS2 targeting miR-135b 96 and miR-31 97 , and miR-375 which regulates YAP1 98 . These microRNAs are reported to have activity in other tissues.…”