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

• Published in: Gynecologic oncology 2012-07, Vol.126 (1), p.124-131
• Main Authors: Choi, Chel Hun, Park, Young-Ae, Choi, Jung-Joo, Song, Taejong, Song, Sang Yong, Lee, Yoo-Young, Lee, Jeong-Won, Kim, Tae-Joong, Kim, Byoung-Gie, Bae, Duk-Soo
• Format: Article
• Language: English
• Subjects: AGTR1; Angiotensin II Type 1 Receptor Blockers - therapeutic use; Combined Modality Therapy; Endometrial carcinoma; Endometrial Neoplasms - genetics; Endometrial Neoplasms - metabolism; Endometrial Neoplasms - pathology; Endometrial Neoplasms - therapy; Female; Hematology, Oncology and Palliative Medicine; Humans; Immunohistochemistry; Losartan; Losartan - therapeutic use; MicroRNA; MicroRNAs - antagonists & inhibitors; MicroRNAs - biosynthesis; MicroRNAs - genetics; Middle Aged; miR-155; Obstetrics and Gynecology; Oligonucleotides, Antisense - administration & dosage; Oligonucleotides, Antisense - genetics; Receptor, Angiotensin, Type 1 - biosynthesis; Receptor, Angiotensin, Type 1 - genetics; Receptors, Angiotensin - genetics; Receptors, Angiotensin - metabolism; Sequence Analysis, DNA; Transfection
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2012.04.020

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.