Molecular Characteristics of Bladder Tumor: Increased Gene Expression of MAGE-A6 and MAGE-A11 with Decreased MicroRNA-34a and MicroRNA-125b

Azin Aghamajidi; Zahra Ousati Ashtiani; Monireh Mohsenzadegan; Nader Tajik; Mahmood Ghafoori Yazdi; Laleh Sharifi; Mohammad Reza Nowroozi

doi:10.18502/ijaai.v21i5.11043

Azin Aghamajidi Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Zahra Ousati Ashtiani Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Monireh Mohsenzadegan Department of Medical Laboratory Science, Faculty of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran
Nader Tajik Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Mahmood Ghafoori Yazdi Uro-Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran
Laleh Sharifi Uro-Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran
Mohammad Reza Nowroozi Uro-Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/ijaai.v21i5.11043

Keywords: Bladder cancer; Immunotherapy; MAGE-A6; MAGE-A11; MicroRNA-34a; MicroRNA-125b

Abstract

Bladder cancer is recognized as one of the top ten most common cancers worldwide. Activation of oncogenes, inactivation of tumor suppressor genes, and dysregulation of androgen signaling pathways are three major pathophysiological causes in the development of bladder tumors. Discovering potential biomarkers is required for the management and immunotherapy of bladder cancer. Melanoma-associated antigen (MAGE)-A6 and MAGE-A11 are two cancer-testis antigens that are potential coregulators of androgen receptors. MicroRNAs, especially miR-34a and miR-125b are two important tumor suppressors that play a critical role in regulating different signaling pathways and inhibiting tumor development.

Twenty-nine surgical tissue biopsies were collected from patients with no preoperative chemotherapy or radiotherapy (26 males and, 3 females, mean age±SD: 62.4±13.3 years). Seventeen adjacent uninvolved tissues with no abnormalities upon histological examination were considered normal controls (14 males and, 3 females, mean age±SD: 64.2±7.4 years) . Quantitative PCR was performed to evaluate the gene expression level of MAGE-A6, MAGE-A11, miR-34a, and miR-125b in bladder cancer biopsies.

MAGE-A6 and MAGE-A11 expressions were significantly increased in bladder tumors compared with normal tissues. However, the expression levels of miR-34a and miR-125b were significantly downregulated in bladder tumor tissues. Interestingly, the expression level of all these genes was significantly associated with tumor grade, pathological stage (pT), and muscular invasion.

MAGE-A6 and MAGE-A11 can be considered potential markers for the diagnosis and immunotherapy of bladder tumors. Furthermore, the modulation of miR-34a and miR-125b gene expression in association with increased MAGE-A6 and MAGE-A11 genes could open a new horizon in the improvement of bladder cancer.