Identification of associated microRNAs in bone destruction of breast cancer bone metastasis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16357
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Kobe University
• Principal Investigator: Kawkami Yohei 神戸大学, 医学研究科, 医学研究員 (50626570)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: がん骨転移 / エクソソーム / miRNA / 破骨細胞 / 骨破壊

Outline of Final Research Achievements

In the present study, the roles of miRNAs in bone destruction caused by breast cancer metastasis were investigated in vitro and in vivo. Our findings indicate that osteolytic factors derived from breast cancer cells stimulated the osteoclast differentiation and function, and that the effects could be regulated positively by miR-16, but negatively by miR-133a or miR-223. Consistent with these in vitro results, in vivo experiments using a breast cancer bone metastasis animal model demonstrated that miR-16 enhanced bone destruction with increased osteoclast activities; in contrast, miR-133a and miR-223 prevented the destruction with decreased activities. In conclusion, the present study demonstrated that miR-16 may enhance bone destruction caused by breast cancer bone metastasis by promoting osteoclast function via increased expressions of osteoclast differentiation markers and osteolytic factors, while miR-133a and miR-223 may suppress this process.

Free Research Field

再生医療

Academic Significance and Societal Importance of the Research Achievements

多くのがん種においてがん細胞が、miRNAやタンパク質を含むエクソソームを放出し、腫瘍産生、がんの進行、遠隔転移に関わる可能性が報告されており“エクソソーム(miRNA)に着目したliquid biopsy”は次世代のがんの診断治療には欠かせない研究分野であると言える。本研究が対象としているいまだ不明な骨転移メカニズムの解明、早期診断、治療への応用という点で、我々が先駆者となりうると確信するとともに研究的・学術的意義が非常に高いと考える。今後のがん治療研究分野において、がん骨転移、骨破壊を診断、制御する事は革新的な領域を創造することになるという点で意義深いと考える。