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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 miR-221 inhibitor or miR-222 inhibitor on expression of SIRT1 protein.(A) Expression of SIRT1 protein levels in PC-3 cells after transfection were determined by Western blot analysis. (B) Quantitation of SIRT1 protein expression. Data represent the mean value ± SEM from three separate experiments. *P<0.05 vs pEX-5, ##P<0.01 vs pEX-5.
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pone.0098833-g006: Effect of miR-221 inhibitor or miR-222 inhibitor on expression of SIRT1 protein.(A) Expression of SIRT1 protein levels in PC-3 cells after transfection were determined by Western blot analysis. (B) Quantitation of SIRT1 protein expression. Data represent the mean value ± SEM from three separate experiments. *P<0.05 vs pEX-5, ##P<0.01 vs pEX-5.

Mentions: Western blot analysis demonstrated that the SIRT1 protein levels of cells transfected with miR-221 inhibitor and miR-222 inhibitor were markedly increased compared with those of cells transfected with pEX-5 (P<0.05 and P<0.01, respectively) (Figures 6A and B). However, there were no significant differences in mRNA levels (Date was shown in Figure S2).


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 miR-221 inhibitor or miR-222 inhibitor on expression of SIRT1 protein.(A) Expression of SIRT1 protein levels in PC-3 cells after transfection were determined by Western blot analysis. (B) Quantitation of SIRT1 protein expression. Data represent the mean value ± SEM from three separate experiments. *P<0.05 vs pEX-5, ##P<0.01 vs pEX-5.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0098833-g006: Effect of miR-221 inhibitor or miR-222 inhibitor on expression of SIRT1 protein.(A) Expression of SIRT1 protein levels in PC-3 cells after transfection were determined by Western blot analysis. (B) Quantitation of SIRT1 protein expression. Data represent the mean value ± SEM from three separate experiments. *P<0.05 vs pEX-5, ##P<0.01 vs pEX-5.
Mentions: Western blot analysis demonstrated that the SIRT1 protein levels of cells transfected with miR-221 inhibitor and miR-222 inhibitor were markedly increased compared with those of cells transfected with pEX-5 (P<0.05 and P<0.01, respectively) (Figures 6A and B). However, there were no significant differences in mRNA levels (Date was shown in Figure S2).

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