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Controlling RECK miR21 Promotes Tumor Cell Invasion and Is Related to Biochemical Recurrence in Prostate Cancer.

Leite KR, Reis ST, Viana N, Morais DR, Moura CM, Silva IA, Pontes J, Katz B, Srougi M - J Cancer (2015)

Bottom Line: We defined different as an expression level greater or less than 1.1 with p<0.05.Transfection of miR-21 using lipid based assay in DU145 cell line, showed decrease in expression of RECK resulting in increase in expression of MMP9.We conclude that miR-21 overexpression is related to increased biochemical recurrence after surgical treatment of prostate cancer.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Medical Research, LIM55, Urology Department, University of Sao Paulo Medical School, Sao Paulo, Brazil.

ABSTRACT
The search for biomarkers to characterize prostate cancer aggressiveness has been the objective for the majority of researchers involved with the most prevalent tumor in men. MiRNAs are important for the control of many cellular functions and their deregulation is involved with tumor development and progression. To find miRNAs differentially expressed in prostate cancer and their relation to prognostic factors and biochemical recurrence we studied 53 surgical specimens from men who underwent radical prostatectomy, through a microarray analysis using the microarray platform (GeneChip® miRNA Array - Affymetrix) with more than 46,000 probes and 847 mature human miRNAs and transcripts. We defined different as an expression level greater or less than 1.1 with p<0.05. The validation study using qRT-PCR had confirmed miR21 as overexpressed in tumor that have recurred with a risk of 2.5. Transfection of miR-21 using lipid based assay in DU145 cell line, showed decrease in expression of RECK resulting in increase in expression of MMP9. Invasion assay with Matrigel showed increase in tumor cell invasion after miR-21 transfection. We conclude that miR-21 overexpression is related to increased biochemical recurrence after surgical treatment of prostate cancer. And the negative control of RECK results in overexpression of MMP9 promotes increasing tumor cell invasion supporting miR-21 as an oncomiR related to aggressiveness in prostate cancer.

No MeSH data available.


Related in: MedlinePlus

The Kaplan-Meier curve shows that miR-21 expression levels greater than 0.64 are significantly related to biochemical recurrence (p=0.003). The Cox regression model revealed that only miR-21 expression is independently related to tumor recurrence with a 2.5 risk.
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Figure 2: The Kaplan-Meier curve shows that miR-21 expression levels greater than 0.64 are significantly related to biochemical recurrence (p=0.003). The Cox regression model revealed that only miR-21 expression is independently related to tumor recurrence with a 2.5 risk.

Mentions: Considering that miR-21 was overexpressed in recurrent tumors and its role has already been described in other neoplasias we also proceed with the validation study of its expression by qRT-PCR 11. In prostate cancer there are only two clinical studies relating miR-21 with biochemical recurrence and with resistance to docetaxel-based chemotherapy 12 13. We analyzed miR-21 through qRT-PCR in 51 cases from the test group (included in the microarray analysis) and in 76 additional cases. Validation through qRT-PCR confirmed that miR-21 overexpression was related to biochemical recurrence. The mean expression for miR-21 in recurrent tumors was 7.20 compared with 2.21 in non-recurrent tumors (p=0.014). A Kaplan-Meier curve was generated, which indicated that expression levels greater than 0.64 were significantly related to biochemical recurrence (p=0.003) (Figure 2). Including Gleason grade <7 and ≥7, preoperatory PSA level < 10 ng/ml and ≥ 10 ng/ml and pT2 and pT3 tumors the Cox regression model revealed that only miR-21 expression was independently related to tumor recurrence with a 2.5 risk.


Controlling RECK miR21 Promotes Tumor Cell Invasion and Is Related to Biochemical Recurrence in Prostate Cancer.

Leite KR, Reis ST, Viana N, Morais DR, Moura CM, Silva IA, Pontes J, Katz B, Srougi M - J Cancer (2015)

The Kaplan-Meier curve shows that miR-21 expression levels greater than 0.64 are significantly related to biochemical recurrence (p=0.003). The Cox regression model revealed that only miR-21 expression is independently related to tumor recurrence with a 2.5 risk.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4317766&req=5

Figure 2: The Kaplan-Meier curve shows that miR-21 expression levels greater than 0.64 are significantly related to biochemical recurrence (p=0.003). The Cox regression model revealed that only miR-21 expression is independently related to tumor recurrence with a 2.5 risk.
Mentions: Considering that miR-21 was overexpressed in recurrent tumors and its role has already been described in other neoplasias we also proceed with the validation study of its expression by qRT-PCR 11. In prostate cancer there are only two clinical studies relating miR-21 with biochemical recurrence and with resistance to docetaxel-based chemotherapy 12 13. We analyzed miR-21 through qRT-PCR in 51 cases from the test group (included in the microarray analysis) and in 76 additional cases. Validation through qRT-PCR confirmed that miR-21 overexpression was related to biochemical recurrence. The mean expression for miR-21 in recurrent tumors was 7.20 compared with 2.21 in non-recurrent tumors (p=0.014). A Kaplan-Meier curve was generated, which indicated that expression levels greater than 0.64 were significantly related to biochemical recurrence (p=0.003) (Figure 2). Including Gleason grade <7 and ≥7, preoperatory PSA level < 10 ng/ml and ≥ 10 ng/ml and pT2 and pT3 tumors the Cox regression model revealed that only miR-21 expression was independently related to tumor recurrence with a 2.5 risk.

Bottom Line: We defined different as an expression level greater or less than 1.1 with p<0.05.Transfection of miR-21 using lipid based assay in DU145 cell line, showed decrease in expression of RECK resulting in increase in expression of MMP9.We conclude that miR-21 overexpression is related to increased biochemical recurrence after surgical treatment of prostate cancer.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Medical Research, LIM55, Urology Department, University of Sao Paulo Medical School, Sao Paulo, Brazil.

ABSTRACT
The search for biomarkers to characterize prostate cancer aggressiveness has been the objective for the majority of researchers involved with the most prevalent tumor in men. MiRNAs are important for the control of many cellular functions and their deregulation is involved with tumor development and progression. To find miRNAs differentially expressed in prostate cancer and their relation to prognostic factors and biochemical recurrence we studied 53 surgical specimens from men who underwent radical prostatectomy, through a microarray analysis using the microarray platform (GeneChip® miRNA Array - Affymetrix) with more than 46,000 probes and 847 mature human miRNAs and transcripts. We defined different as an expression level greater or less than 1.1 with p<0.05. The validation study using qRT-PCR had confirmed miR21 as overexpressed in tumor that have recurred with a risk of 2.5. Transfection of miR-21 using lipid based assay in DU145 cell line, showed decrease in expression of RECK resulting in increase in expression of MMP9. Invasion assay with Matrigel showed increase in tumor cell invasion after miR-21 transfection. We conclude that miR-21 overexpression is related to increased biochemical recurrence after surgical treatment of prostate cancer. And the negative control of RECK results in overexpression of MMP9 promotes increasing tumor cell invasion supporting miR-21 as an oncomiR related to aggressiveness in prostate cancer.

No MeSH data available.


Related in: MedlinePlus