Functional analysis of OCIAD2 localized at mitochondria in lung adenocarcinoma

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K07455
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: University of Tsukuba
• Principal Investigator: Shib Aya 筑波大学, 医学医療系, 准教授 (50708427)
• Project Period (FY): 2021-01-01 – 2024-03-31
• Keywords: 肺腺癌 / アポトーシス / ミトコンドリア / OCIAD2

Outline of Final Research Achievements

OCIAD2 is a gene that is overexpressed in invasive lung adenocarcinoma and exhibits very high tumor specificity because it is not expressed in normal lung tissue. The high-expression group has significantly poorer prognosis compared to the low-expression group, suggesting that OCIAD2 may have some function in the malignancy of lung adenocarcinoma. In this study, we focused on the function of OCIAD2 in mitochondria and analyzed the effects of OCIAD2 expression inhibition on proliferation and apoptosis using lung adenocarcinoma cells in vitro. OCIAD2 is suggested to inhibit apoptosis by stabilizing the mitochondrial membrane potential in multiple lung adenocarcinoma cells, and it was revealed to interact with numerous mitochondrial localization proteins. The interaction with VDAC1 is particularly intriguing, and further analysis of the molecular mechanisms of OCIAD2 function will be conducted in the future.

Free Research Field

分子病理学

Academic Significance and Societal Importance of the Research Achievements

OCIAD2は浸潤性肺腺癌で高発現するミトコンドリア局在タンパク質であるが、その詳細な機能と分子メカニズムは明らかではなかった。本課題では、肺腺癌細胞でのOCIAD2の発現抑制が細胞増殖を抑制しミトコンドリア依存性アポトーシスを引き起こすことを見出し、その機能に重要と考えられる新たな結合タンパク質も同定した。今後は、OCIAD2が結合相手の1つであるVDAC1とどのように作用するかを解析し、この結合を阻害して腫瘍進展を抑制する治療戦略を開発したい。これにより、OCIAD2-VDAC1複合体またはOCIAD2-その他の結合相手を標的とした抗腫瘍薬が肺腺癌の有望な治療法となる可能性がある。