MicroRNA Expression and Cancer Stem Cell Markers in Urinary Bladder Cancer A Correlative Study

Abstract

Accumulating data have suggested the role of miRNAs in the molecular pathogenesis of cancer. The chromosomal coding sites of oncogenic miRNAs exhibit negative regulation of the tumour suppressor genes and may further lead to urinary bladder cancer. Therefore, bladder tumours usually express oncogenic miRNAs and have suppressed expression of tumour suppressor miRNAs. Contrarily, tumour suppressor miRNAs are found to be located in the fragile region where chromosomal aberrations are very common. This initiates the upregulation of the target oncogenes. Several cancer stem cell markers have been recently identified that are regulated by these miRNAs or vice-versa. Lately studied cellular mechanisms have suggested that the upregulation of miRNA-21 and the downregulation of miRNA-145 with tumorigenesis induce the expression of cancer stem cell markers such as CD44, Nanog and Oct 4. Furthermore, cancer stem cells and miRNAs are suggested to be the important driving factors of bladder tumor initiation, differentiation, apoptosis, proliferation and drug resistance. newlineA total of 138 patients were enrolled in the study and as controls 36 bladder tissue specimens of benign prostatic hyperplasia patients who underwent retropubic prostatectomy for treatment were taken into consideration. Newly diagnosed cases with complete clinical data and age and#8805;30 years were included in the study. While patients with any other secondary malignancy or who were being treated were excluded from the study. All the patients registered in the study, were followed up to 60 months for bladder tumour recurrence and survival. The follow-up procedures included cystoscopy, urine cytology, renal ultrasonography, CT/MRI and a bone scan. newlineImmunohistochemistry was performed in this planned study to determine the protein expression of CSC markers. The primary antibodies used were CD44 (BioGenex, U.S.A.), Oct-4 (Proteintech, U.S.A) and Nanog (Proteintech, U.S.A.). The tissue sections were first subjected to dewaxing in 3 changes of xylene (each for 5 minutes) fol