p53在單胺氧化酶B抑制腎細胞癌疾病進展之角色

何岩¹、簡銘賢²、林雍偉^1,3

臺北市立萬芳醫院-委託臺北醫學大學辦理 泌尿科¹

臺北醫學大學-醫學院-臨床醫學研究所²
臺北醫學大學-醫學院-醫學系-泌尿學科³

The Role of p53 in Monoamine Oxidase B Inhibition of Renal Cell Carcinoma Progression
Yen Ho¹, Ming-Hsien Chien², Yung-Wei Lin^1,3

Department of Urology, Wan Fang Hospital, Taipei Medical University¹

Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University²

Department of Urology, School of Medicine, College of Medicine, Taipei Medical University³

Purpose: This study aims to explore the role of monoamine oxidase B (MAOB), an enzyme known for its role in neurotransmitter metabolism, in the progression of renal cell carcinoma (RCC), particularly clear cell RCC (ccRCC). Given that RCC often resists conventional treatments, new molecular insights are needed to identify effective prognostic markers and therapeutic targets.

Materials and Methods: The expression levels of MAOB were compared between RCC and normal renal tissues using immunohistochemistry and Western blot analyses. Functional assays were conducted on RCC cell lines to investigate the impact of MAOB on cell proliferation, migration, and apoptosis, using both enzyme-active and enzyme-dead mutants of MAOB. Additionally, RCC xenografts in mice were used to assess the tumor-suppressive effects of MAOB in vivo. Mechanistic studies focused on the role of MAOB in modulating reactive oxygen species (ROS) and p53 activity, with measurements taken via ROS assays and p53 stabilization studies.

Results: MAOB expression was significantly elevated in RCC tissues compared to normal renal tissue, with higher levels correlating to advanced tumor grades and stages. Functional assays showed that MAOB overexpression promoted RCC cell proliferation and migration, while MAOB inhibition, achieved through siRNA knockdown and pharmacological inhibitors, led to a marked reduction in cell growth and invasiveness. Additionally, MAOB was linked to increased ROS production, which activated tumorigenic pathways like PI3K/AKT. These findings suggest MAOB plays a crucial role in RCC progression through ROS-mediated signaling pathways.

Conclusion: This study suggests that MAOB suppresses RCC progression by increasing ROS and stabilizing p53, leading to reduced tumor growth. MAOB may serve as a promising prognostic marker and therapeutic target for RCC.