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Gynecol Oncol. 2012 Jul;126(1):124-31. doi: 10.1016/j.ygyno.2012.04.020. Epub 2012 Apr 21.

Angiotensin II type I receptor and miR-155 in endometrial cancers: synergistic antiproliferative effects of anti-miR-155 and losartan on endometrial cancer cells.

Author information

1
Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Abstract

OBJECTIVE:

MicroRNA-155 (miR-155) is one of the micro RNAs (miRNA) most consistently involved in neoplastic diseases, and it is known to repress the angiotensin II type 1 receptor (AGTR1). The aim of the present study was to evaluate the expressions of miR-155 and AGTR1, and to clarify the potential efficacy of anti-miR-155, alone and in combination with AGTR1 blocker losartan in endometrial cancers.

METHODS:

Expressions of miR-155 and AGTR1 were evaluated using real-time PCR and immunohistochemistry. And the MTT assay was performed in endometrial cancer cells following anti-miR-155 and AGTR1 blocker (losartan) treatment, alone and in combination.

RESULTS:

miR-155 was over-expressed and AGTR1 was underexpressed in endometrial carcinoma tissues. AGTR1 immunoreactivity was found in six of ten (60.0%) normal endometrium, 11 of 14 (78.6%) endometrial hyperplasia, and 27 of 62 (43.5%) endometrial carcinoma tissues (P=0.051), and patients with AGTR1 expression showed trend towards improved survival after multivariate analysis (P=0.08). We checked that abolishing the function of miR-155 and AGTR1 by anti-miR-155 or losartan inhibited cell survival of endometrial carcinoma cells, respectively, and furthermore, combined treatment showed synergistic effects.

CONCLUSIONS:

In this study, we characterized the expressions of miR-155 and AGTR1 in endometrial tissues. The combined treatment with anti-miR-155 and losartan has a synergistic antiproliferative effect and an improved understanding is required to clarify whether miR-155 and AGTR1 can be used as a novel therapeutic target in endometrial cancer.

PMID:
22525818
DOI:
10.1016/j.ygyno.2012.04.020
[Indexed for MEDLINE]

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