In silico analysis of biomarker potentials of miRNA-mediated ceRNAs in prostate cancer

Objective: The objective of this study is to define novel biomarkers for Prostate Cancer (PCa) via in silico analysis thattakes PCa-specific miRNAs, finds their combinatorial target genes (potential ceRNAs), selects ones containingTranscribed Ultra Conserved Region (T-UCR) among them and potentiates their relevance with PCa.Methods: Thirty-four miRNAs of which clinical relevances with PCa were proved experimentally were exported viamiRWalk database.Using the ComiR database, 859 genes targeted by these 34 miRNAs simultaneously were identified.Genes with ComiR score above 0.911 were taken into account. Genes containing T-UCR and showing potential ceRNAactivity were extracted. Among PCa-associated ceRNAs including T-UCR, we identified genes with significantexpression differences between PCa and normal prostate tissue using the GEPIA database. The statistical evaluation ofthe association of NFAT5 and PTBP2 genes with PCa was performed by Spearman correlation test in GEPIA database.Results: PCa-associated ceRNAs cross-matching with genes including T-UCR in their exonic regions were NFAT5,CLK3, PTBP2, CPEB4, MIPOL1 and TCF4. We identified genes with significant expression differences between PCa andnormal prostate tissues among PCa-associated ceRNAs including T-UCR. According to this analysis, NFAT5 and PTBP2genes were significantly less expressed in PCa than in normal prostate tissue while the others didn’t show anysignificant differential expression pattern. NFAT5 and PTBP2 genes were found to be significantly associated with PCa(p=0.000012; R=0.72). Conclusion: All in all, this is the study associating NFAT5 and PTBP2 genes with PCa and giving them tumorsuppressive potential for PCa. Still, larger and more comprehensive studies are needed on this issue.

Prostat kanserinde miRNA aracılıklı ceRNA’ların biyobelirteç potansiyellerinin in siliko analizi

Amaç: Bu çalışmanın amacı, PK’ye özgü miRNA’ları tespit edip, onların kombinatoryal olarak hedefledikleri genleri (potansiyel ceRNA'lar) bulup, aralarından T-UCR içerenleri seçip, bunların istatistiksel korelasyon yöntemleri ile PK ile olan ilişkilerini değerlendiren in siliko analiz yoluyla PK için yeni biyobelirteçler tanımlamaktır. Yöntemler: Klinik olarak PK ile ilişkisi deneysel olarak ispatlanmış 34 miRNA miRWalk veri tabanı kullanılarak tespit edildi. ComiR veri tabanı kullanılarak, bu 34 miRNA tarafından eş zamanlı olarak hedeflenen 859 gen tanımlandı. ComiR skoru 0.911'in üzerinde olan genler dikkate alındı. T-UCR içeren ve ceRNA aktivitesi gösteren genler bulunmuştur. T-UCR içeren PK ile ilişkili ceRNA'lar arasında, GEPIA veritabanı kullanılarak PK ve normal prostat dokusu arasındaki belirgin ekspresyon farklılıklarına sahip olan genler tanımlandı. NFAT5 ve PTBP2 genlerinin PK ile ilişkisinin istatistiksel değerlendirmesi, GEPIA veri tabanında Pearson korelasyon testi ile gerçekleştirildi. Bulgular: Eksonik bölgelerinde T-UCR içeren genler PK-ilişkili ceRNA'lar NFAT5, CLK3, PTBP2, CPEB4, MIPOL1 ve TCF4 genleri olarak tespit edildi. T-UCR içeren PK ile ilişkili ceRNA'lar arasında PCa ve normal prostat dokuları arasında belirgin ekspresyon farklılıklarına sahip genleri tanımladık. Bu analize göre, NFAT5 ve PTBP2 genleri, PK'de normal prostat dokusundan çok daha az eksprese edilirken, diğerleri ifade düzeyi açısından anlamlı bir farklılık göstermemiştir. NFAT5 ve PTBP2 gen çiftinin PK ile anlamlı derecede ilişkili olduğunu bulduk (p = 0.000012; R = 0.72). Sonuç: Sonuç olarak, bu çalışma PK ile NFAT5 ve PTBP2 genlerini ilişkilendiren ve bu genlere PK için tümör baskılayıcı fonksiyon öngören ilk çalışmadır. Yine de, bu konuda daha geniş ve daha kapsamlı çalışmalara ihtiyaç vardır.

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