Maria Mirela Iacob, Costin Petcu, Tatiana Vassu-Dimov and Ileana Constantinescu
Aim: Bladder cancer is known to be the ninth most common cancer worldwide. Current diagnostic and prognostic tools are insufficient to predict clinical outcome and response to personalized therapy. Carcinogenesis mechanisms involve genetic and epigenetic pathways. The aim of this research was to develop optimal experimental condition to assess the expression of selected miR-145-3p, miR-145-5p, miR-152 and miR-182 in patients with urinary bladder tumors, in order to correlate this with the tumor clinic routine characteristics. This approach would add more information on the etiology of bladder cancer tumors in an attempt to elaborate molecular algorithm.
Methods: This work approaches epigenetic modifications in order to investigate the dynamics of certain tissue extracted microRNA species expression correlated with particular tumor characteristics. We have selected: miR-145-3p, miR-145-5p, miR-152 and miR-182 to be evaluated in terms of their expression in tumor tissues samples. A number of 71 Romanian patients undergoing investigations for urinary bladder cancer were introduced in our study. Their clinical characteristics were correlated with the microRNAs expressions in cancer tissues and normal urinary bladder tissues. Upregulation and down regulation of selected microRNAs was revealed using quantitative TaqMan based real-time reverse transcription PCR (RT-qPCR) (Applied Biosystems USA). Data analysis was performed by using 2-ΔΔCT method and Student’s t-test.
Results: We have found different expression profiles showing down regulation for the miR-145-3p, miR-145-5p, miR-152 and upregulation of miR-182. The clinical significance of this profile has emphasized that the investigated bladder tumors have a distinct genetic fingerprint with an impact on pathology and prognosis of the patients. Different mechanisms are involved for significantly reduced expression level of miRNAs in bladder cancers: genetic alterations and Single Nucleotide Polymorphism (SNP), epigenetic silencing and defects in the miRNA biogenesis pathway.
Conclusions: Our preliminary results show that selected miRNAs are differently expressed in cancer tissue samples from selected patients in comparison with normal bladder tissues. This epigenetic profile could be used for early diagnosis, response to treatment and prognosis of urinary bladder tumors.