title: Angiotensin II type I receptor and miR-155 in endometrial cancers: synergistic antiproliferative effects of anti-miR-155 and losartan on endometrial cancer cells.
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.
authors.affiliation: Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Chel Hun
authors.initials: CH
authors.lastname: Choi
authors.forename: Young-Ae
authors.initials: YA
authors.lastname: Park
authors.forename: Jung-Joo
authors.initials: JJ
authors.lastname: Choi
authors.forename: Taejong
authors.initials: T
authors.lastname: Song
authors.forename: Sang Yong
authors.initials: SY
authors.lastname: Song
authors.forename: Yoo-Young
authors.initials: YY
authors.lastname: Lee
authors.forename: Jeong-Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Tae-Joong
authors.initials: TJ
authors.lastname: Kim
authors.forename: Byoung-Gie
authors.initials: BG
authors.lastname: Kim
authors.forename: Duk-Soo
authors.initials: DS
authors.lastname: Bae
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019808:Losartan / Q000627:therapeutic use*; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage* / Q000235:genetics; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis* / Q000235:genetics; D011945:Receptors, Angiotensin / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014162:Transfection
chemical_list: C544065:AGTR1 protein, human; D047228:Angiotensin II Type 1 Receptor Blockers; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D019808:Losartan