MicroRNA-101 Inhibits Growth of Epithelial Ovarian Cancer by Relieving Chromatin-Mediated Transcriptional Repression of p21(waf1/cip1)

作者：Semaan Assaad; 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^*

来源：Pharmaceutical Research, 2011, 28(12): 3079-3090.

DOI：10.1007/s11095-011-0547-x

• enhancer of zeste homolog 2 (EzH2)
• epithelial ovarian cancer (EOC)
• microRNA-101miR-101
• p21(waf1/cip1)
• RNA interference (RNAi)

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.

• 出版日期2011-12