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

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• 作者：Chel Hun Choi^a ; ¹ ; Young-Ae Park^a ; ¹ ; Jung-Joo Choi^a ; Taejong Song^b ; Sang Yong Song^c ; Yoo-Young Lee^a ; Jeong-Won Lee^a ; Tae-Joong Kim^a ; Byoung-Gie Kim^a ; Duk-Soo Bae^a ; ^{huna0@naver.com}
• 关键词：MicroRNA ; miR-155 ; AGTR1 ; Losartan ; Endometrial carcinoma
• 刊名：Gynecologic Oncology
• 出版年：2012
• 期刊代码：295_00908258
• 类别：med
• 出版时间：July, 2012
• 卷：126
• 期：1
• 页码：124-131
• 文件大小：972 K

摘要

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.