1. Academic Validation
  2. BTN3A3 inhibits clear cell renal cell carcinoma progression by regulating the ROS/MAPK pathway via interacting with RPS3A

BTN3A3 inhibits clear cell renal cell carcinoma progression by regulating the ROS/MAPK pathway via interacting with RPS3A

  • Cell Signal. 2023 Oct 6:112:110914. doi: 10.1016/j.cellsig.2023.110914.
Zhangyun Li 1 Mengmeng Zhang 1 Sihan Chen 2 Weiyu Dong 1 Rui Zong 1 Yanyan Wang 3 Shaohua Fan 4
Affiliations

Affiliations

  • 1 School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu, China.
  • 2 Central Laboratory, Institute of Dermatology, Chinese Academy of Medical Science & Peking Union Medical College, Nanjing, Jiangsu, China.
  • 3 Department of Ultrasonic Medicine, The First People's Hospital of Xuzhou, Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou, Jiangsu, China. Electronic address: lulizhan335@126.com.
  • 4 School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu, China. Electronic address: 6020040121@jsnu.edu.cn.
Abstract

Butyrophilin subfamily 3 member A3 (BTN3A3) is a member of the immunoglobulin superfamily and functions as a tumor suppressor in multiple Cancer types. Our study has revealed that in clear cell renal cell carcinoma (ccRCC), patients who express high levels of BTN3A3 experience longer survival times than those with lower expression. Further, we have observed that BTN3A3 inhibits the proliferation, migration, and invasion of ccRCC cells. Through the utilization of an immunoprecipitation assay followed by mass spectrometry, we have discovered that BTN3A3 binds directly to RPS3A. Knockdown of BTN3A3 led to increased cell proliferation, migration, and invasion. However, this effect was significantly reduced when RPS3A was simultaneously overexpressed. Previous reports have demonstrated that RPS3A positively regulates mitochondrial function and Reactive Oxygen Species (ROS) levels. Our study has shown that overexpression of both BTN3A3 and RPS3A can increase cellular oxygen consumption rate (OCR) and ROS levels. Furthermore, we have observed that the addition of H2O2 can reverse the effects of BTN3A3 knockdown on cell proliferation and migration by increasing the cellular ROS level. ROS play a crucial role in regulating the MAPK pathway and tumor cell growth. To further explore this relationship, we examined RNA-Seq and immunoblotting data and found that BTN3A3 can negatively regulate the degree of activation of the MAPK signaling pathway. This finding suggests that the BTN3A3/RPS3A complex may regulate ccRCC progression by modulating MAPK pathways. Therefore, BTN3A3 could serve as both a prognostic marker and a potential therapeutic target for ccRCC patients.

Keywords

BTN3A3; EMT; MAPK; ROS; RPS3A.

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