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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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Effect of down-regulation of SIRT1 on PC-3 cell migration.(A) A transwell assay was used to measure the migration of cells transfected with pGPU6 or pGPU6-siSIRT1. (B) Number of cells penetrated the insert membrane. Data represent the mean value ± SEM from three separate experiments. *P<0.05 vs pGPU6.
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pone.0098833-g009: Effect of down-regulation of SIRT1 on PC-3 cell migration.(A) A transwell assay was used to measure the migration of cells transfected with pGPU6 or pGPU6-siSIRT1. (B) Number of cells penetrated the insert membrane. Data represent the mean value ± SEM from three separate experiments. *P<0.05 vs pGPU6.

Mentions: SIRT1 expression was significantly suppressed in cells transfected with siSIRT1 compared with those transfected with pGPU6 as a control (Figure 7A). There were no significant differences in cell proliferation between cells transfected with siSIRT1 and pGPU6 (Figure 7B). However, cells transfected with siSIRT1 resulted in a two-fold reduction in the apoptosis rate compared with that in cells transfected with pGPU6 (P<0.01) (Figures 8A and B). Interestingly, the migration of cells transfected with siSIRT1 was significantly increased compared with that of cells transfected with pGPU6 (P<0.05) (Figures 9A and B).


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)

Effect of down-regulation of SIRT1 on PC-3 cell migration.(A) A transwell assay was used to measure the migration of cells transfected with pGPU6 or pGPU6-siSIRT1. (B) Number of cells penetrated the insert membrane. Data represent the mean value ± SEM from three separate experiments. *P<0.05 vs pGPU6.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0098833-g009: Effect of down-regulation of SIRT1 on PC-3 cell migration.(A) A transwell assay was used to measure the migration of cells transfected with pGPU6 or pGPU6-siSIRT1. (B) Number of cells penetrated the insert membrane. Data represent the mean value ± SEM from three separate experiments. *P<0.05 vs pGPU6.
Mentions: SIRT1 expression was significantly suppressed in cells transfected with siSIRT1 compared with those transfected with pGPU6 as a control (Figure 7A). There were no significant differences in cell proliferation between cells transfected with siSIRT1 and pGPU6 (Figure 7B). However, cells transfected with siSIRT1 resulted in a two-fold reduction in the apoptosis rate compared with that in cells transfected with pGPU6 (P<0.01) (Figures 8A and B). Interestingly, the migration of cells transfected with siSIRT1 was significantly increased compared with that of cells transfected with pGPU6 (P<0.05) (Figures 9A and B).

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