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Molecular Cancer
Published in: Molecular Cancer 1/2014

Open Access 01-12-2014 | Research

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

Authors: Takashi Mitamura, Hidemichi Watari, Lei Wang, Hiromi Kanno, Makiko Kitagawa, Mohamed Kamel Hassan, Taichi Kimura, Mishie Tanino, Hiroshi Nishihara, Shinya Tanaka, Noriaki Sakuragi

Published in: Molecular Cancer | Issue 1/2014

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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.
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Metadata
Title
microRNA 31 functions as an endometrial cancer oncogene by suppressing Hippo tumor suppressor pathway
Authors
Takashi Mitamura
Hidemichi Watari
Lei Wang
Hiromi Kanno
Makiko Kitagawa
Mohamed Kamel Hassan
Taichi Kimura
Mishie Tanino
Hiroshi Nishihara
Shinya Tanaka
Noriaki Sakuragi
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2014
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-13-97

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