caa a22 4500 445312556 CHVBK 20180317142635.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s11095-011-0547-x doi (NATIONALLICENCE)springer-10.1007/s11095-011-0547-x MicroRNA-101 Inhibits Growth of Epithelial Ovarian Cancer by Relieving Chromatin-Mediated Transcriptional Repression of p21waf1/cip1 [Elektronische Daten] [Assaad Semaan, Aamer Qazi, Shelly Seward, Sreedhar Chamala, Christopher Bryant, Sanjeev Kumar, Robert Morris, Christopher Steffes, David Bouwman, Adnan Munkarah, Donald Weaver, Scott Gruber, Ramesh Batchu] ABSTRACT: Purpose: MicroRNA-101 (miR-101) expression is negatively associated with tumor growth and proliferation in several solid epithelial cancers. Enhancer of zeste homolog 2 (EzH2) appears to be a functional target of miR-101. We explore the role of miR-101 and its interaction with EzH2 in epithelial ovarian carcinoma (EOC). Methods: In situ hybridization (ISH) for miR-101 was performed on EOC patient tissues and normal controls. EOC cell lines were transfected with miR-101 and subjected to growth analysis and clonogenic assays. Cell motility was assessed by Boyden chamber and wound-healing assays. P21waf1/cip1 and EzH2 interaction was assessed by Chromatin Immunoprecipitation (ChIP) assay in MDAH-2774 cells. SCID mice were assessed for tumor burden after injection with miR-101 or control vector-treated MDAH-2774 cells. Results: ISH analysis revealed a decrease in miR-101 expression in EOC compared with normal tissue. MiR-101 re-expression in EOC cell lines resulted in increased apoptosis, decreased cellular proliferation, invasiveness, and reduced growth of tumor xenografts. CHIP assays revealed that re-expression of miR-101 inhibited the interaction of EzH2 with p21waf1/cip1 promoter. Conclusions: MiR-101 re-expression appears to have antitumor effects, providing a better understanding of the role of miR-101 in EOC. Springer Science+Business Media, LLC, 2011 enhancer of zeste homolog 2 (EzH2) nationallicence epithelial ovarian cancer (EOC) nationallicence microRNA-101miR-101 nationallicence p21 waf1/cip1 nationallicence RNA interference (RNAi) nationallicence Semaan Assaad Laboratory of Surgical Oncology & Developmental Therapeutics Department of Surgery, Wayne State University, 48201, Detroit, Michigan, USA aut Qazi Aamer Laboratory of Surgical Oncology & Developmental Therapeutics Department of Surgery, Wayne State University, 48201, Detroit, Michigan, USA aut Seward Shelly Laboratory of Surgical Oncology & Developmental Therapeutics Department of Surgery, Wayne State University, 48201, Detroit, Michigan, USA aut Chamala Sreedhar Laboratory of Surgical Oncology & Developmental Therapeutics Department of Surgery, Wayne State University, 48201, Detroit, Michigan, USA aut Bryant Christopher MD Anderson Cancer Center Orlando, Gynecologic Oncology, 32806, Orlando, Florida, USA aut Kumar Sanjeev Division of Gynecologic Surgery, Mayo Clinic Cancer Center, 55905, Rochester, Minnesota, USA aut Morris Robert Department of Ob/Gyn, Wayne State University, 48201, Detroit, Michigan, USA aut Steffes Christopher Laboratory of Surgical Oncology & Developmental Therapeutics Department of Surgery, Wayne State University, 48201, Detroit, Michigan, USA aut Bouwman David Laboratory of Surgical Oncology & Developmental Therapeutics Department of Surgery, Wayne State University, 48201, Detroit, Michigan, USA aut Munkarah Adnan Department of Women's Health Services, Henry Ford Health System, 48202, Detroit, Michigan, USA aut Weaver Donald Laboratory of Surgical Oncology & Developmental Therapeutics Department of Surgery, Wayne State University, 48201, Detroit, Michigan, USA aut Gruber Scott John D. Dingell VA Medical Center, 48201, Detroit, Michigan, USA aut Batchu Ramesh Laboratory of Surgical Oncology & Developmental Therapeutics Department of Surgery, Wayne State University, 48201, Detroit, Michigan, USA aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/12(2011-12-01), 3079-3090 0724-8741 28:12<3079 2011 28 11095 https://doi.org/10.1007/s11095-011-0547-x text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0547-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Semaan Assaad Laboratory of Surgical Oncology & Developmental Therapeutics Department of Surgery, Wayne State University, 48201, Detroit, Michigan, USA aut NATIONALLICENCE 700 1- Qazi Aamer Laboratory of Surgical Oncology & Developmental Therapeutics Department of Surgery, Wayne State University, 48201, Detroit, Michigan, USA aut NATIONALLICENCE 700 1- Seward Shelly Laboratory of Surgical Oncology & Developmental Therapeutics Department of Surgery, Wayne State University, 48201, Detroit, Michigan, USA aut NATIONALLICENCE 700 1- Chamala Sreedhar Laboratory of Surgical Oncology & Developmental Therapeutics Department of Surgery, Wayne State University, 48201, Detroit, Michigan, USA aut NATIONALLICENCE 700 1- Bryant Christopher MD Anderson Cancer Center Orlando, Gynecologic Oncology, 32806, Orlando, Florida, USA aut NATIONALLICENCE 700 1- Kumar Sanjeev Division of Gynecologic Surgery, Mayo Clinic Cancer Center, 55905, Rochester, Minnesota, USA aut NATIONALLICENCE 700 1- Morris Robert Department of Ob/Gyn, Wayne State University, 48201, Detroit, Michigan, USA aut NATIONALLICENCE 700 1- Steffes Christopher Laboratory of Surgical Oncology & Developmental Therapeutics Department of Surgery, Wayne State University, 48201, Detroit, Michigan, USA aut NATIONALLICENCE 700 1- Bouwman David Laboratory of Surgical Oncology & Developmental Therapeutics Department of Surgery, Wayne State University, 48201, Detroit, Michigan, USA aut NATIONALLICENCE 700 1- Munkarah Adnan Department of Women's Health Services, Henry Ford Health System, 48202, Detroit, Michigan, USA aut NATIONALLICENCE 700 1- Weaver Donald Laboratory of Surgical Oncology & Developmental Therapeutics Department of Surgery, Wayne State University, 48201, Detroit, Michigan, USA aut NATIONALLICENCE 700 1- Gruber Scott John D. Dingell VA Medical Center, 48201, Detroit, Michigan, USA aut NATIONALLICENCE 700 1- Batchu Ramesh Laboratory of Surgical Oncology & Developmental Therapeutics Department of Surgery, Wayne State University, 48201, Detroit, Michigan, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/12(2011-12-01), 3079-3090 0724-8741 28:12<3079 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer