Sex determining region Y-box 2 (SOX2), and Nanog homebox (NANOG) are stem re¬lated transcription factors, that confer self- renewal and pluripotency properties to embryonic stem cells (ESCs) and cancer stem cells (CSCs). So, the expression signature of the stemness state of primary tumors could be valuable for identifying patients who are most likely to suffer more aggressive tumor course or develop metastases and may also represent a promising molecular target for future therapeutic approaches. Evaluating the role of miRNAs as regulators of human malignancies represents an interesting research field. In this study we hypothesized that miR-143 may regulate bladder carcinogenesis, through regulating CSC markers (NANOG and SOX2). The expression of miR-143 was assessed in relation to the stemness markers Nanog and SOX2 in bladder cancer tissues and bladder carcinoma cell line. We also highlighted the possible association of our target genes expression with the clinicopathological features of BC patients.
Material &Methods: The present study included 27 tissue specimens from bladder cancer patients and 10 specimens from control subjects. In addition, human bladder cancer cell line (T24) and normal bladder epithelium cell line (HL14/12) were also studied. Reverse transcription quantitative Polymerase chain reaction (RT-qPCR) was used to assess gene expression of miR-143, SOX2 and NANOG. The expression of NANOG and SOX2 proteins was also detected by immunohistochemical staining in urinary bladder tissues from BC and control groups.
Results: miR-143 expression was significantly downregulated, while NANOG and SOX2 were significantly upregulated, in BC patients when compared to control group. miR-143 showed significant negative correlation with tumor grade, invasiveness, expression of NANOG and SOX2. Nanog and SOX2 mRNA were significantly elevated in tumor with higher grades, muscle invasive stages and showed significant positive correlation with each other. Downregulated miR-143, and upregulated Nanog and Sox2 could significantly predict muscle-invasive bladder cancer in crude and adjusted models.
Conclusion: miR-143 may have a role in regulating the NANOG and SOX2 stemness factors as shown by the significant negative correlation between miR-143 & both Nanog and Sox2 but the exact mechanisms of this role need to be further explored. Our study provides further proof of the pivotal role played by miRNAs in regulating the characteristics of CSCs in many tumors.