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Down-regulation of mir-221 and mir-222 restrain prostate cancer cell proliferation and migration that is partly mediated by activation of SIRT1.

Yang X, Yang Y, Gan R, Zhao L, Li W, Zhou H, Wang X, Lu J, Meng QH - PLoS ONE (2014)

Bottom Line: MiR-221 and miR-222 were highly expressed in PC-3 cells compared with in LNCap cells.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.These effects are potentially mediated by up-regulation of SIRT1.

View Article: PubMed Central - PubMed

Affiliation: Wenzhou Medical University School of Laboratory Medicine and Life Sciences, Wenzhou, Zhejiang, China.

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.

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Related in: MedlinePlus

Regulation of SIRT1 by miR-221 and miR-222.(A) The complementary binding sites of miR-221 and miR-222 on SIRT1-3′UTR predicted by miRanda database. (B) Luciferase activity was carried out to verify the binding and interaction of miR-221 and miR-222 with SIRT1. There were no differences in luciferase activity among the groups (P>0.05). Data represent the mean value ± SEM from three separate experiments.
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pone.0098833-g010: Regulation of SIRT1 by miR-221 and miR-222.(A) The complementary binding sites of miR-221 and miR-222 on SIRT1-3′UTR predicted by miRanda database. (B) Luciferase activity was carried out to verify the binding and interaction of miR-221 and miR-222 with SIRT1. There were no differences in luciferase activity among the groups (P>0.05). Data represent the mean value ± SEM from three separate experiments.

Mentions: As the miRanda data show, miR-221 and miR-222 bound to one of the target sequences located in the 3′-UTR of SIRT1 mRNA (Figure 10A). To ascertain the direct interaction between miR-221 or miR-222 and SIRT1 mRNA-3′UTR, luciferase activity assay was conducted. However, luciferase activities revealed no statistically significant differences in miR-221 or miR-222 level in PC-3 cells co-transfected with SIRT1-3′UTR binding sequence reporter plasmid compared with the control (Figure 10B). In other words, miR-221 and miR-222 did not bind to the SIRT1 sequence directly and did not exert a direct biological interaction.


Down-regulation of mir-221 and mir-222 restrain prostate cancer cell proliferation and migration that is partly mediated by activation of SIRT1.

Yang X, Yang Y, Gan R, Zhao L, Li W, Zhou H, Wang X, Lu J, Meng QH - PLoS ONE (2014)

Regulation of SIRT1 by miR-221 and miR-222.(A) The complementary binding sites of miR-221 and miR-222 on SIRT1-3′UTR predicted by miRanda database. (B) Luciferase activity was carried out to verify the binding and interaction of miR-221 and miR-222 with SIRT1. There were no differences in luciferase activity among the groups (P>0.05). Data represent the mean value ± SEM from three separate experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4043919&req=5

pone.0098833-g010: Regulation of SIRT1 by miR-221 and miR-222.(A) The complementary binding sites of miR-221 and miR-222 on SIRT1-3′UTR predicted by miRanda database. (B) Luciferase activity was carried out to verify the binding and interaction of miR-221 and miR-222 with SIRT1. There were no differences in luciferase activity among the groups (P>0.05). Data represent the mean value ± SEM from three separate experiments.
Mentions: As the miRanda data show, miR-221 and miR-222 bound to one of the target sequences located in the 3′-UTR of SIRT1 mRNA (Figure 10A). To ascertain the direct interaction between miR-221 or miR-222 and SIRT1 mRNA-3′UTR, luciferase activity assay was conducted. However, luciferase activities revealed no statistically significant differences in miR-221 or miR-222 level in PC-3 cells co-transfected with SIRT1-3′UTR binding sequence reporter plasmid compared with the control (Figure 10B). In other words, miR-221 and miR-222 did not bind to the SIRT1 sequence directly and did not exert a direct biological interaction.

Bottom Line: MiR-221 and miR-222 were highly expressed in PC-3 cells compared with in LNCap cells.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.These effects are potentially mediated by up-regulation of SIRT1.

View Article: PubMed Central - PubMed

Affiliation: Wenzhou Medical University School of Laboratory Medicine and Life Sciences, Wenzhou, Zhejiang, China.

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.

Show MeSH
Related in: MedlinePlus