Identification and characterization of PRELID2 as a novel molecular target gene for renal cell carcinoma therapy

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K18618
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Iwate Medical University
• Principal Investigator: Renpei Kato 岩手医科大学, 医学部, 講師 (60748234)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 腎癌 / PRELID2 / ミトコンドリア / ROS

Outline of Final Research Achievements

We evaluated a critical role in renal carcinogenesis for PRELID2 which is exclusively up-regulated in clear cell RCC (ccRCC) cases. Introduction of PRELID2 into HEK293 cells significantly enhanced cell growth, whereas knockdown of PRELID2 expression drastically suppressed growth of ccRCC cells. Notably, depletion of PRELID2 led to enhance ROS production.　Moreover, downregulation of spare respiratory capacity was observed in PRELID2-depleted cells by extracellular flux analysis. We further demonstrated that exogeneous HA-PRELID2 interacted with endogenous mitochondrial molecular X.
These findings suggest that PRELID2 might play a crucial role in mitochondrial ROS regulation for renal carcinogenesis, and be promising therapeutic target for ccRCC therapy.

Free Research Field

腎癌

Academic Significance and Societal Importance of the Research Achievements

PRELID2に関する分子機能はこれまでほとんど解明されておらず、共同研究者の片桐教授が腎癌における癌特異分子であることを初めて発見した。その後、我々はPRELID2のミトコンドリア機能との関連を証明し、PRELID2に結合するミトコンドリア関連分子を同定している。本研究と現在進めている基盤Cの研究を通じて、世界に先駆けて癌化と関連するPRELID2の生理機能を報告し、腎癌の新しい治療標的分子を捉えられる可能性があると考える。