1. MicroRNA-34a: a key regulator in the hallmarks of renal cell carcinoma
Eman A. Toraih1*, Afaf T. Ibrahiem2, Manal S. Fawzy1*, Mohammad H. Hussein3, Saeed Awad M. Al-Qahtani4, Aly A. M. Shaalan1,4
1 Faculty of Medicine, Suez Canal University, 2 Faculty of Medicine, Mansoura University, Egypt, 3 Faculty of Medicine, Cairo University, Egypt , 4 Faculty of Medicine, Jazan University, Saudi Arabia
Introduction
Results
Results (continued)
Renal cell carcinoma (RCC) incidence has increased over the past two decades with unpredictable long-term morbidity and mortality. Recent studies reported microRNAs (miRNAs) as promising biomarkers for early cancer detection and accurate prognosis as well as targets for more efficient treatment. However, although their evident role in cancer biology, their tissue specificity and complex biology makes it difficult to understand their specific role in the disease process and the genes affected by their deregulation.
This study aimed to evaluate the expression levels of miR- 34a and 11 of its bioinformatically-selected target genes and proteins with the highest significant levels to test their potential deregulation in RCC to better understand the molecular mechanisms that underlie the tumorigenesis and progression of this type of cancer.
Gene expression profiling revealed a significant overexpression of miR-34a, MET and E2F3 and down-regulation of TP53INP2 and SOX2 genes in RCC patients, Fig. 2. Most specimens expressed markers for apoptosis (Bcl2 and Tp53 protein), and cell proliferation and differentiation (TGFB1), and angiogenesis (VEGFA).
Table 1. ROC analysis for evaluating diagnostic performance
Fig.8. Correlation analysis of miR-34a with targets.
Fig.3. Structural analysis of miRNA-34a gene locus and transcripts
Fig.4. Schematic representation of the targets and predicted miR-34 binding sites
Fig. 1. miR-34a target genes regulating the hallmarks of cancer. Genes are analyzed by IHC (blue) and RT-PCR (yellow).
Fig. 9. Gene expression and clinico-pathological features
Fig. 10. Protein expression and clinico-pathological features
Fig. 6. Immunohistochemistry markers of miR-34a putative target proteins in RCC specimens
Fig. 11. Protein-protein interaction using STRING network analysis
Fig. 2. Predicted Target Genes of miRNA-34a in Renal cell carcinoma pathway.
Conclusions
Methods and Materials
The study results suggested that miR-34a along with its putative target genes could represent potential therapeutic molecular targets in renal cell carcinoma. The exact molecular interplay between the potential miR-34a target genes will warrant further detailed studies.
Quantitative real-time PCR for miR-34a and its targets; MET oncogene, genes regulating apoptosis (TP53INP2, DFFA), cell proliferation (E2F3), and cell differentiation (SOX2, TGFB3) as well as immunohistochemical assay for VEGFA, TP53, Bcl2, TGFB1 and Ki67 protein expression have been performed in 85 FFPE renal tumor specimens obtained from patients with various histopathological types and diverse pathological outcomes. In addition, in silico network analysis of these molecular markers have been analyzed.
Contact
Eman A. Toraih:
Manal S. Fawzy:
Fig.5. Gene expression profile.
Fig.7. Protein expression profile.