Öz
Objective:
The objective of this study is to define novel biomarkers for Prostate Cancer
(PCa) via in silico analysis that takes PCa-specific miRNAs, finds their
combinatorial target genes (potential ceRNAs), selects ones containing
Transcribed 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 via miRWalk 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 ceRNA activity were extracted. Among PCa-associated ceRNAs
including T-UCR, we identified genes with significant expression differences between
PCa and normal prostate tissue using the GEPIA database. The statistical
evaluation of the 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 and normal prostate tissues
among PCa-associated ceRNAs including T-UCR. According to this analysis, NFAT5
and PTBP2 genes were significantly less expressed in PCa than in normal
prostate tissue while the others didn’t show any significant 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 tumor suppressive potential for PCa. Still, larger and more
comprehensive studies are needed on this issue.
Anahtar Kelimeler
Kaynakça
- 1. Yikilmaz TN, Öztürk E. Yüksek Riskli Prostat Kanserinde Radikal Prostatektomi/Radical Prostatectomy In High-Risk Prostate Cancer. Dicle Med J. 2016; 43 :419.
- 2. Saydam F, Değirmenci İ, Güneş HV. MicroRNAs and cancer. Dicle Med J. 2011; 38 :113-20.
- 3. Ergun S, Oztuzcu S. Oncocers: ceRNA-mediated cross-talk by sponging miRNAs in oncogenic pathways. Tumor Biol. 2015; 36 :3129-36.
- 4. Zhou J, Wang R, Zhang J, et al. Conserved expression of ultra-conserved noncoding RNA in mammalian nervous system. BBA-Gene Regul Mech. 2017; 1860 :1159-68.
- 5. Bodakçi MN, Bozkurt Y, Atar M, et al. The results of transrectal prostate biopsy in patients with low levels of prostate specific antigen. Dicle Med J. 2012; 39.
- 6. Dweep H, Gretz N. miRWalk2. 0: a comprehensive atlas of microRNA-target interactions. Nat Methods. 2015; 12 :697-.
- 7. Coronnello C, Benos PV. ComiR: combinatorial microRNA target prediction tool. Nucleic Acids Res. 2013; 41(W1): W159-W64.
- 8. Bejerano G, Pheasant M, Makunin I, et al. Ultraconserved elements in the human genome. Science. 2004; 304(5675): 1321-5.
- 9. Tang Z, Li C, Kang B, et al. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017; 45(W1): W98-W102.
- 10. Ediz C, İhvan AN, Hayit H, et al. Positive Predictive Values in Diagnosis of Incidental Prostate Cancer. Dicle Med J. 2016; 43.
- 11. Cheung CY, Ko BC. NFAT5 in cellular adaptation to hypertonic stress–regulations and functional significance. J Mol Signal. 2013; 8 :5.
- 12. Küper C, Beck F-X, Neuhofer W. NFAT5-mediated expression of S100A4 contributes to proliferation and migration of renal carcinoma cells. Front Physiol. 2014; 5: 293.
- 13. Amara S, Alotaibi D, Tiriveedhi V. NFAT5/STAT3 interaction mediates synergism of high salt with IL-17 towards induction of VEGF-A expression in breast cancer cells. Oncol Lett. 2016; 12 :933-43.
- 14. Guo K, Jin F. NFAT5 promotes proliferation and migration of lung adenocarcinoma cells in part through regulating AQP5 expression. Biochem Bioph Res Co. 2015; 465 :644-9.
- 15. Chen M, Sastry SK, O'Connor KL. Src kinase pathway is involved in NFAT5-mediated S100A4 induction by hyperosmotic stress in colon cancer cells. Am J Physiol-Cell Ph. 2011; 300 :C1155-C63.
- 16. Qin X, Wang Y, Li J, et al. NFAT5 inhibits invasion and promotes apoptosis in hepatocellular carcinoma associated with osmolality. Neoplasma. 2017; 64 :502-10.
- 17. Licatalosi DD, Yano M, Fak JJ, et al. Ptbp2 represses adult-specific splicing to regulate the generation of neuronal precursors in the embryonic brain. Gene Dev. 2012; 26 :1626-42.
- 18. He X, Pool M, Darcy K, et al. Knockdown of polypyrimidine tract-binding protein suppresses ovarian tumor cell growth and invasiveness in vitro. Oncogene. 2007; 26 :4961.
- 19. Ji Q, Zhang L, Liu X, et al. Long non-coding RNA MALAT1 promotes tumour growth and metastasis in colorectal cancer through binding to SFPQ and releasing oncogene PTBP2 from SFPQ/PTBP2 complex. Brit J Cancer. 2014; 111 :736.
- 20. Cheung HC, Hai T, Zhu W, et al. Splicing factors PTBP1 and PTBP2 promote proliferation and migration of glioma cell lines. Brain. 2009; 132 :2277-88.
- 21. Agatheeswaran S, Singh S, Biswas S, et al. BCR-ABL mediated repression of miR-223 results in the activation of MEF2C and PTBP2 in chronic myeloid leukemia. Leukemia. 2013; 27 :1578.
- 22. Lou S, Ji J, Cheng X, et al. Oncogenic miR‑132 sustains proliferation and self‑renewal potential by inhibition of polypyrimidine tract‑binding protein 2 in glioblastoma cells. Mol Med Rep. 2017; 16 :7221-8.
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Bölüm | Araştırma Yazıları |
| Yazarlar | |
| Yayımlanma Tarihi | 13 Aralık 2018 |
| Gönderilme Tarihi | 15 Aralık 2018 |
| Yayımlandığı Sayı | Yıl 2018 Cilt: 45 Sayı: 4 |