EZH2-specific microRNA-98 inhibits human ovarian cancer stem cell proliferation via regulating the pRb-E2F pathway.
The Polycomb group protein, enhancer of zeste homolog 2 (EZH2), plays an important role in transcriptional regulation through chromatin remodeling and interactions with other transcription factors to control cell proliferation and embryonic development. Previous study has shown that EZH2 is important for cell cycle regulation and is highly expressed in human ovarian cancer. Loss of EZH2 inhibits growth of ovarian cancer as well as other human carcinomas. In this study, an expression plasmid of EZH2-targeted microRNA-98 was constructed and transfected into human ovarian cancer stem cells (OCSCs). Seventy-two hours after transfection, cell growth was inhibited and arrested at the G0/G1 transition. p21(CIPI/WAF1) was up-regulated, while the CDK2/cyclin E complex and c-Myc were down-regulated. Most importantly, expression levels of E2F1, retinoblastoma protein (pRb), and histone deacetylase 1 (HDAC1) in the pRb-E2F signaling pathway had changed. Furthermore, microRNA-98 suppressed the growth of OCSCs xenograft tumors. Our findings suggest that EZH2-specific microRNA-98 can effectively inhibit cell proliferation in vitro and regulate the pRb-E2F pathway in human OCSCs.
Shanghai Tenth People's Hospital, Medical School, Tongji University, Shanghai, 200072, China, liutelt@163.com.
Te
T
Liu
Lengchen
L
Hou
Yongyi
Y
Huang
D000328:Adult; D000818:Animals; D049109:Cell Proliferation; D019927:Cyclin E / Q000235:genetics; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors / Q000235:genetics*; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D016193:G1 Phase / Q000235:genetics; D064593:Heterografts; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D063151:Polycomb Repressive Complex 2 / Q000235:genetics*; D016160:Retinoblastoma Protein / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
C475820:CCNE1 protein, human; D019927:Cyclin E; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; C546084:MIRN98 microRNA, human; D035683:MicroRNAs; D015513:Oncogene Proteins; D016160:Retinoblastoma Protein; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2