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

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

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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.

Original languageEnglish
Article number97
JournalMolecular Cancer
Volume13
Issue number1
DOIs
Publication statusPublished - 2014 Apr 29
Externally publishedYes

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Keywords

  • cyclin D1
  • Endometrial cancer
  • Hippo pathway
  • LATS2
  • microRNA 31

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

Cite this

Mitamura, T., Watari, H., Wang, L., Kanno, H., Kitagawa, M., Hassan, M. K., Kimura, T., Tanino, M., Nishihara, H., Tanaka, S., & Sakuragi, N. (2014). MicroRNA 31 functions as an endometrial cancer oncogene by suppressing Hippo tumor suppressor pathway. Molecular Cancer, 13(1), [97]. https://doi.org/10.1186/1476-4598-13-97