MicroRNA-101 Inhibits Growth of Epithelial Ovarian Cancer by Relieving Chromatin-Mediated Transcriptional Repression of p21waf1/cip1

Autor: Donald W. Weaver, Christopher S. Bryant, Ramesh B. Batchu, Adnan R. Munkarah, Scott A. Gruber, Christopher P. Steffes, David L. Bouwman, Sanjeev Kumar, Aamer Qazi, Robert W. Morris, Shelly Seward, Sreedhar Chamala, Assaad Semaan
Rok vydání: 2011
Předmět:
Zdroj: Pharmaceutical Research. 28:3079-3090
ISSN: 1573-904X
0724-8741
DOI: 10.1007/s11095-011-0547-x
Popis: 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). 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. 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. MiR-101 re-expression appears to have antitumor effects, providing a better understanding of the role of miR-101 in EOC.
Databáze: OpenAIRE
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