title: Down-regulation of mir-221 and mir-222 restrain prostate cancer cell proliferation and migration that is partly mediated by activation of SIRT1.
abstract: Studies have shown that miR-221 and miR-222 are deregulated in many cancers, including prostate cancer. Nevertheless, the biological role and the underlying mechanisms of miR-221 and miR-222 in the pathogenesis of androgen-independent prostate cancer are still not clear. The proliferation, apoptosis, cell cycle distinction, and migration capacity of prostate cells were determined following transfection of miR-221 or miR-222 inhibitor. The biological impact and regulation of SIRT1 on prostate cancer cells were investigated. MiR-221 and miR-222 were highly expressed in PC-3 cells compared with in LNCap cells. After miR-221 or miR-222 expression was inhibited, the proliferation and migration rates of PC-3 cells decreased and the apoptosis rate increased. Moreover, SIRT1 protein was up-regulated in cells after they were transfected with miR-221 or miR-222 inhibitor. Cells transfected with siSIRT1 showed increased migration and a decreased apoptosis rate, but there was no significant effect on cell proliferation compared with the controls. There was a negative correlation between miR-221 or miR-222 and SIRT1, but no direct target relationship was identified. These data demonstrate that miR-221 and miR-222 are highly expressed in PC-3 cells. Their inhibition leads to reduced cell proliferation and migration and increased apoptosis in prostate cancer cells. These effects are potentially mediated by up-regulation of SIRT1.
authors.affiliation: Wenzhou Medical University School of Laboratory Medicine and Life Sciences, Wenzhou, Zhejiang, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.affiliation: Wenzhou Medical University School of Laboratory Medicine and Life Sciences, Wenzhou, Zhejiang, China.
authors.forename: Yingmei
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Wenzhou Medical University School of Laboratory Medicine and Life Sciences, Wenzhou, Zhejiang, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Gan
authors.affiliation: Wenzhou Medical University School of Laboratory Medicine and Life Sciences, Wenzhou, Zhejiang, China.
authors.forename: Lingxu
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Wenzhou Medical University School of Laboratory Medicine and Life Sciences, Wenzhou, Zhejiang, China; Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou, Zhejiang, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Wenzhou Medical University School of Laboratory Medicine and Life Sciences, Wenzhou, Zhejiang, China; Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou, Zhejiang, China.
authors.forename: Huaibin
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Wenzhou Medical University School of Laboratory Medicine and Life Sciences, Wenzhou, Zhejiang, China; Department of Clinical Laboratory Medicine, Jinhua People's Hospital, Jinhua, Zhejiang, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Wenzhou Medical University School of Laboratory Medicine and Life Sciences, Wenzhou, Zhejiang, China; Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou, Zhejiang, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Qing H
authors.initials: QH
authors.lastname: Meng
mesh_terms: D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D056564:Sirtuin 1; C525709:MIR221, human; C525710:MIR222, human; C447939:SIRT1 protein, human