PBRM1拮抗EZH2抑制膀胱癌进展的机制研究

Bladder cancer is one of the most common genitourinary malignancies in the world. Low-grade non-muscle invasive tumours recur frequently and easy to progress, whereas muscle-invasive tumours frequently metastasize. Although conventional clinical variables, such as the tumor stage, grade, tumor size, number of tumors are generally regarded as prognostic factors, how to predict tumor progression remains a challenge. EZH2, a catalytic subunit of the polycomb repressive complex 2 (PRC2), High levels of EZH2 often correlate with tumor stage and poor prognosis. Studies have shown that SWI/SNF complex with EZH2 role in antagonism. Our previous studies have found that lower the express PBRM1 gene in bladder cancer, the function of tumor suppressor, and act as independent factors of prognosis of bladder cancer. PBRM1 is an important subunit in the SWI/SNF complex, has the function of target gene expression in bladder cancer in low, the function of tumor suppressor genes. Therefore, we suggest PBRM1 function antagonism EZH2, play an important role in the progress in bladder cancer. Therefore, we can further analyze antagonistic relationship between PBRM1 and EZH2 in regulating the recurrence and progress of bladder cancer and further investigate molecular mechanism, provide new targets for diagnosis and treatment and molecular markers for prediction progress in bladder cancer.

膀胱癌是男性泌尿生殖系统最常见的恶性肿瘤，其中，非肌层浸润性膀胱癌具有易复发、易进展的特点，而肌层浸润性膀胱癌容易转移。然而，膀胱癌复发及进展的机制仍不清楚，常见预后因子如肿瘤分期、分级、大小、数量等，对肿瘤复发及进展的预测仍是一个难题。EZH2是PRC2复合体中重要的催化亚基。在膀胱癌中，EZH2高表达与肿瘤侵袭性和进展相关。我们前期研究发现PBRM1基因在膀胱癌中低表达，发挥抑癌基因的功能，并且能够作为膀胱癌预后的独立因素。PBRM1是SWI/SNF复合体中重要的亚基，具有引导SWI/SNF靶向结合特异性基因的功能。SWI/SNF复合体被证实与EZH2呈拮抗作用。因此，我们深入解析PBRM1可能拮抗EZH2调控膀胱癌复发及进展的分子机制，为肿瘤诊断及治疗提供新的靶点，为预测膀胱癌进展提供分子标记物。