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MicroRNA-302a Suppresses Tumor Cell Proliferation by Inhibiting AKT in Prostate Cancer.

Zhang GM, Bao CY, Wan FN, Cao DL, Qin XJ, Zhang HL, Zhu Y, Dai B, Shi GH, Ye DW - PLoS ONE (2015)

Bottom Line: Cell proliferation and cell cycle analysis were performed on PCa cells that stably expressed miRNA-302a.Overexpression of miRNA-302a induced G1/S cell cycle arrest in PCa cells, and suppressed PCa cell proliferation both in vitro and in vivo.Furthermore, miRNA-302a inhibits AKT expression by directly binding to its 3΄ untranslated region, resulting in subsequent alterations of the AKT-GSK3β-cyclin D1 and AKT-p27Kip1 pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

ABSTRACT
Micro (mi) RNAs are important regulators involved in various physical and pathological processes, including cancer. The miRNA-302 family has been documented as playing a critical role in carcinogenesis. In this study, we investigated the role of miRNA-302a in prostate cancer (PCa). MiRNA-302a expression was detected in 44 PCa tissues and 10 normal prostate tissues, and their clinicopathological significance was analyzed. Cell proliferation and cell cycle analysis were performed on PCa cells that stably expressed miRNA-302a. The target gene of miRNA-302a and the downstream pathway were further investigated. Compared with normal prostate tissues, miRNA-302a expression was downregulated in PCa tissues, and was even lower in PCa tissues with a Gleason score ≥8. Overexpression of miRNA-302a induced G1/S cell cycle arrest in PCa cells, and suppressed PCa cell proliferation both in vitro and in vivo. Furthermore, miRNA-302a inhibits AKT expression by directly binding to its 3΄ untranslated region, resulting in subsequent alterations of the AKT-GSK3β-cyclin D1 and AKT-p27Kip1 pathway. These results reveal miRNA-302a as a tumor suppressor in PCa, suggesting that miRNA-302a may be used as a potential target for therapeutic intervention in PCa.

No MeSH data available.


Related in: MedlinePlus

Overexpression of miRNA-302a in PCa cells triggers alterations in the AKT-GSK3β-cyclin D1 and AKT-p27Kip1signaling pathways.Western blot analyses showed downregulated AKT, phosphorylated AKT (pAKT) and cyclin D1 levels, and upregulated GSK3β,pGSK3β and p27Kip1 levels in miRNA-302a overexpressing PCa cells. PI3K levels were not affected.
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pone.0124410.g006: Overexpression of miRNA-302a in PCa cells triggers alterations in the AKT-GSK3β-cyclin D1 and AKT-p27Kip1signaling pathways.Western blot analyses showed downregulated AKT, phosphorylated AKT (pAKT) and cyclin D1 levels, and upregulated GSK3β,pGSK3β and p27Kip1 levels in miRNA-302a overexpressing PCa cells. PI3K levels were not affected.

Mentions: To detect the molecular mechanisms by which miRNA-302a exerts its posttranscriptional regulatory functions, we used bioinformatics algorithms (http://www.targetscan.org) to seek possible target genes, and found that the 3΄UTR of AKT mRNA harbors a conserved binding site for miRNA-302a. Next, we examined the expression of AKT at the mRNA and protein level in PC-3-302a and DU145-302a cells and controls. As shown in Figs 5A and 6, compared with controls, AKT expressions decreased significantly in PC-3-302a and DU145-302a cells, at both the mRNA and protein level. Furthermore, AKT expression in PC-3-302a tumors was significantly lower than in PC-3-Scr tumors, as determined by real-time PCR and IHC staining (Fig 5B and 5C). These results suggest that AKT expression is downregulated by miRNA-302a in PCa.


MicroRNA-302a Suppresses Tumor Cell Proliferation by Inhibiting AKT in Prostate Cancer.

Zhang GM, Bao CY, Wan FN, Cao DL, Qin XJ, Zhang HL, Zhu Y, Dai B, Shi GH, Ye DW - PLoS ONE (2015)

Overexpression of miRNA-302a in PCa cells triggers alterations in the AKT-GSK3β-cyclin D1 and AKT-p27Kip1signaling pathways.Western blot analyses showed downregulated AKT, phosphorylated AKT (pAKT) and cyclin D1 levels, and upregulated GSK3β,pGSK3β and p27Kip1 levels in miRNA-302a overexpressing PCa cells. PI3K levels were not affected.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4414271&req=5

pone.0124410.g006: Overexpression of miRNA-302a in PCa cells triggers alterations in the AKT-GSK3β-cyclin D1 and AKT-p27Kip1signaling pathways.Western blot analyses showed downregulated AKT, phosphorylated AKT (pAKT) and cyclin D1 levels, and upregulated GSK3β,pGSK3β and p27Kip1 levels in miRNA-302a overexpressing PCa cells. PI3K levels were not affected.
Mentions: To detect the molecular mechanisms by which miRNA-302a exerts its posttranscriptional regulatory functions, we used bioinformatics algorithms (http://www.targetscan.org) to seek possible target genes, and found that the 3΄UTR of AKT mRNA harbors a conserved binding site for miRNA-302a. Next, we examined the expression of AKT at the mRNA and protein level in PC-3-302a and DU145-302a cells and controls. As shown in Figs 5A and 6, compared with controls, AKT expressions decreased significantly in PC-3-302a and DU145-302a cells, at both the mRNA and protein level. Furthermore, AKT expression in PC-3-302a tumors was significantly lower than in PC-3-Scr tumors, as determined by real-time PCR and IHC staining (Fig 5B and 5C). These results suggest that AKT expression is downregulated by miRNA-302a in PCa.

Bottom Line: Cell proliferation and cell cycle analysis were performed on PCa cells that stably expressed miRNA-302a.Overexpression of miRNA-302a induced G1/S cell cycle arrest in PCa cells, and suppressed PCa cell proliferation both in vitro and in vivo.Furthermore, miRNA-302a inhibits AKT expression by directly binding to its 3΄ untranslated region, resulting in subsequent alterations of the AKT-GSK3β-cyclin D1 and AKT-p27Kip1 pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

ABSTRACT
Micro (mi) RNAs are important regulators involved in various physical and pathological processes, including cancer. The miRNA-302 family has been documented as playing a critical role in carcinogenesis. In this study, we investigated the role of miRNA-302a in prostate cancer (PCa). MiRNA-302a expression was detected in 44 PCa tissues and 10 normal prostate tissues, and their clinicopathological significance was analyzed. Cell proliferation and cell cycle analysis were performed on PCa cells that stably expressed miRNA-302a. The target gene of miRNA-302a and the downstream pathway were further investigated. Compared with normal prostate tissues, miRNA-302a expression was downregulated in PCa tissues, and was even lower in PCa tissues with a Gleason score ≥8. Overexpression of miRNA-302a induced G1/S cell cycle arrest in PCa cells, and suppressed PCa cell proliferation both in vitro and in vivo. Furthermore, miRNA-302a inhibits AKT expression by directly binding to its 3΄ untranslated region, resulting in subsequent alterations of the AKT-GSK3β-cyclin D1 and AKT-p27Kip1 pathway. These results reveal miRNA-302a as a tumor suppressor in PCa, suggesting that miRNA-302a may be used as a potential target for therapeutic intervention in PCa.

No MeSH data available.


Related in: MedlinePlus