title: Down-regulation of Dicer and Ago2 is associated with cell proliferation and apoptosis in prostate cancer.
abstract: Dicer and Argonaute2 (Ago2) are critical components responsible not only for RNA interference but also for microRNA synthesis. The present study investigated the roles of Dicer and Ago2 in prostate cancer (Pca). First, the expression levels of Dicer and Ago2 in Pca tissues were determined by immunohistochemistry (IHC) and compared with pathological features. Next, RNA interference was used to down-regulate the expression levels of Dicer and Ago2 in the Pca cell lines LNCaP, PC-3, and DU145, and effects on proliferation, apoptosis, and cell cycle were detected using the CCK-8 assay and flow cytometry, respectively. We found that Dicer and Ago2 expression levels in Pca tissues were higher than those in adjacent benign tissues and correlated with lower Gleason patterns, with the exception of Dicer expression in localized Pca. In vitro, silencing Dicer or Ago2 inhibited cell proliferation and induced apoptosis in LNCaP, PC-3, and DU145, as well as arrested the cell cycle at the G2/M phase in androgen-dependent LNCaP, or at S phase in the androgen-independent PC-3 and DU145. Altogether these findings suggest that Dicer and Ago2 play important roles in proliferation, apoptosis, and the cell cycle in Pca and might serve as both promising biomarkers for Pca progression and potential therapeutic targets.
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, No. 270, Dong'an Road, Shanghai, 200032, China.
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Bian
authors.forename: Gui-Ming
authors.initials: GM
authors.lastname: Zhang
authors.forename: Cheng-Yuan
authors.initials: CY
authors.lastname: Gu
authors.forename: Ying
authors.initials: Y
authors.lastname: Cai
authors.forename: Chao-Fu
authors.initials: CF
authors.lastname: Wang
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Shen
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhu
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Dai
authors.forename: Ding-Wei
authors.initials: DW
authors.lastname: Ye
mesh_terms: D017209:Apoptosis; D060565:Argonaute Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D002453:Cell Cycle; D049109:Cell Proliferation; D053487:DEAD-box RNA Helicases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics; D043244:Ribonuclease III / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: C466422:AGO2 protein, human; D060565:Argonaute Proteins; D014408:Biomarkers, Tumor; D034741:RNA, Small Interfering; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases