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The risks, degree of malignancy and clinical progression of prostate cancer associated with the MDM2 T309G polymorphism: a meta-analysis.

ABSTRACT: To determine the risk, malignant degree and clinical progression of prostate cancer (PCa) associated with mouse double-minute 2 protein (MDM2) T309G variants, a meta-analysis was performed on all eligible published studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess these associations in seven studies that included 5151 cases and 1003 controls. In the overall analysis, the 309G allele was significantly associated with a decreased PCa risk (OR=0.85, 95% CI: 0.74-0.97); this was also the case for the homozygous comparison (OR=0.72, 95% CI: 0.55-0.95) and the dominant genetic model (OR=0.79, 95% CI: 0.65-0.96). The 309G allele was also found to be significantly associated with lower degrees of PCa malignancy (OR=0.85, 95% CI: 0.75-0.96) in the overall analysis, as well as in the heterozygous comparison (OR=0.79, 95% CI: 0.65-0.96), homozygous comparison (OR=0.76, 95% CI: 0.58-0.98) and dominant genetic model (OR=0.81, 95% CI: 0.68-0.96). Furthermore, grouping analysis showed that the 309G allele in Caucasians was significantly correlated with a decreased PCa risk (OR=0.77, 95% CI: 0.61-0.96); this was also the case in the homozygous comparison (OR=0.51, 95% CI: 0.31-0.86). The grouping analysis also showed that the 309G variant in Caucasians was significantly associated with a lower degree of PCa malignancy in all of the genetic models. In addition, we found that the 309G variant in Caucasians was significantly associated with a slower PCa clinical progression in all of the genetic models. In summary, our meta-analysis showed that the MDM2 309G variant was significantly associated with a decreased PCa risk, lower malignant degree and slower clinical progression in Caucasians, but there was no obvious association in the Asian population.

SUBMITTER: Yang J

PROVIDER: S-EPMC3734987 | biostudies-other | 2012 Sep

REPOSITORIES: biostudies-other

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Project description:A growing number of dysregulated long non‑coding (lnc)RNAs have been verified to serve an essential role in human prostate cancer. However, the underlying mechanisms of lncRNA MNX1 Antisense RNA 1 (MNX1‑AS1) in prostate cancer has not been explored. Therefore, the present study aimed to explore the function of MNX1‑AS1 in prostate cancer tumorigenesis and investigate the in‑depth mechanism. The expression of MNX1‑AS1, microRNA (miR)‑2113 and murine double min 2 (MDM2) in prostate cancer tissues and corresponding normal tissues were assessed by reverse transcription‑quantitative PCR. The protein expression levels of MDM2 were detected by western blotting. LNCaP and PC‑3 cells were transfected with short hairpin (sh)‑MNX1‑AS1, miR‑2113 mimics, miR‑2113 inhibitor and pCDH‑MDM2 vector using Lipofectamine® 3000. Cell proliferation, migration and invasion abilities were assessed by CCK‑8 assay, colony formation and Transwell assay, respectively. Dual luciferase reporter assay was carried out to confirm the putative targets of MNX1‑AS1 and miR‑2113. Tumor formation experiment in nude mice was applied to evaluate the tumor growth effect of MNX1‑AS1 in vivo. The expression of MNX1‑AS1 was significantly upregulated in the prostate cancer tissues and cell lines. MNX1‑AS1 knockdown suppressed the abilities of cell viability and migration and invasion in vitro and inhibited tumor growth in vivo. Additionally, luciferase reporter assay revealed that MNX1‑AS1 could target miR‑2113 and negatively interacted with miR‑2113 in prostate cancer cells. miR‑2113 directly targeted to MDM2 and negatively modulated the expression of MDM2. Rescue assays suggested that the viability, migration and invasion of impaired cells triggered by transfection with sh‑MNX1‑AS1 alone could be recovered by co‑transfection with sh‑MNX1‑AS1 + miR‑2113 inhibitor or sh‑MNX1‑AS1 + pCDH‑ MDM2 vector. The present study demonstrated that MNX1‑AS1 promoted prostate cancer progression through regulating miR‑2113/ MDM2 axis.

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The risks, degree of malignancy and clinical progression of prostate cancer associated with the MDM2 T309G polymorphism: a meta-analysis.

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