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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

MiRNA-302a suppresses AKT expression by directly targeting its 3΄ untranslated region.AKT mRNA expression was remarkably suppressed in (A) PC-3-302a and DU145-302a cells, and (B) PC-3-302a tumors (five independent tumors were detected). (C) Immunohistochemistry staining indicated lower expression of AKT in PC-3-302a tumors. (D) Relative luciferase activity was notably suppressed in wild-type AKT-3΄ untranslated region (UTR) transfected cells. (E) Schematic representation of the luciferase reporter, which carried the wild-type or mutant AKT-3’ UTR. (* P<0.05).
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pone.0124410.g005: MiRNA-302a suppresses AKT expression by directly targeting its 3΄ untranslated region.AKT mRNA expression was remarkably suppressed in (A) PC-3-302a and DU145-302a cells, and (B) PC-3-302a tumors (five independent tumors were detected). (C) Immunohistochemistry staining indicated lower expression of AKT in PC-3-302a tumors. (D) Relative luciferase activity was notably suppressed in wild-type AKT-3΄ untranslated region (UTR) transfected cells. (E) Schematic representation of the luciferase reporter, which carried the wild-type or mutant AKT-3’ UTR. (* P<0.05).

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)

MiRNA-302a suppresses AKT expression by directly targeting its 3΄ untranslated region.AKT mRNA expression was remarkably suppressed in (A) PC-3-302a and DU145-302a cells, and (B) PC-3-302a tumors (five independent tumors were detected). (C) Immunohistochemistry staining indicated lower expression of AKT in PC-3-302a tumors. (D) Relative luciferase activity was notably suppressed in wild-type AKT-3΄ untranslated region (UTR) transfected cells. (E) Schematic representation of the luciferase reporter, which carried the wild-type or mutant AKT-3’ UTR. (* P<0.05).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0124410.g005: MiRNA-302a suppresses AKT expression by directly targeting its 3΄ untranslated region.AKT mRNA expression was remarkably suppressed in (A) PC-3-302a and DU145-302a cells, and (B) PC-3-302a tumors (five independent tumors were detected). (C) Immunohistochemistry staining indicated lower expression of AKT in PC-3-302a tumors. (D) Relative luciferase activity was notably suppressed in wild-type AKT-3΄ untranslated region (UTR) transfected cells. (E) Schematic representation of the luciferase reporter, which carried the wild-type or mutant AKT-3’ UTR. (* P<0.05).
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