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PMID: 21818714 Published · ppublish English Journal Article

MicroRNA-101 inhibits growth of epithelial ovarian cancer by relieving chromatin-mediated transcriptional repression of p21(waf¹/cip¹).

Pharmaceutical research ·Vol. 28 ·No. 12 ·2011-12-00 ·Pages 3079-90

Semaan A, Qazi AM, Seward S, Chamala S, Bryant CS, Kumar S, Morris R, Steffes CP, Bouwman DL, Munkarah AR, Weaver DW, Gruber SA, Batchu RB

Abstract

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. P21(waf1/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 p21(waf1/cip1) promoter. MiR-101 re-expression appears to have antitumor effects, providing a better understanding of the role of miR-101 in EOC.

MeSH Terms
Animals Apoptosis Carcinoma, Ovarian Epithelial Cell Line, Tumor Cell Proliferation Chromatin/genetics,metabolism Cyclin-Dependent Kinase Inhibitor p21/genetics,metabolism DNA-Binding Proteins/genetics,metabolism Enhancer of Zeste Homolog 2 Protein Female Gene Expression Regulation, Neoplastic Humans Male Mice Mice, SCID MicroRNAs/genetics,metabolism Neoplasm Invasiveness/genetics,pathology Neoplasms, Glandular and Epithelial/genetics,metabolism,pathology Ovarian Neoplasms/genetics,metabolism,pathology Ovary/metabolism,pathology Polycomb Repressive Complex 2 Transcription Factors/genetics,metabolism
Chemicals
Chromatin Cyclin-Dependent Kinase Inhibitor p21 DNA-Binding Proteins MIRN101 microRNA, human MicroRNAs Transcription Factors EZH2 protein, human Enhancer of Zeste Homolog 2 Protein Polycomb Repressive Complex 2
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Semaan Assaad
Laboratory of Surgical Oncology & Developmental Therapeutics Department of Surgery, Wayne State University, Detroit, Michigan 48201, USA.
Qazi Aamer M
Seward Shelly
Chamala Sreedhar
Bryant Christopher S
Kumar Sanjeev
Morris Robert
Steffes Christopher P
Bouwman David L
Munkarah Adnan R
Weaver Donald W
Gruber Scott A
Batchu Ramesh B
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Article Info
Journal
Pharmaceutical research
Abbr.
Pharm Res
ISSN
1573-904X
DOI
10.1007/s11095-011-0547-x
Published
2011-12-00
Epub
2011-00-05
Pages
3079-90
Language
English
Region
United States
NLM ID
8406521
Subset
IM
External Links
PubMed source DOI: 10.1007/s11095-011-0547-x View journal details
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