日本語フィールド
著者：*Norihisa Uehara, Yukari Kyumoto-Nakamura, Yoshikazu Mikami, Manabu Hayatsu, Soichiro Sonoda, Takayoshi Yamaza, Akiko Kukita, Toshio Kukita題名：miR-92a-3p encapsulated in bone metastatic mammary tumor cell-derived extracellular vesicles modulates mature osteoclast longevity 発表情報：Cancer Sci 巻: 113 号: 12 ページ: 4219-4229キーワード：apoptosis; breast cancer; extracellular vesicles; miRNA; osteoclast概要：Aberrant osteoclast formation and activation are the hallmarks of osteolytic metastasis. Extracellular vesicles (EVs), released from bone metastatic tumor cells, play a pivotal role in the progression of osteolytic lesions. However, the mechanisms through which tumor cell-derived EVs regulate osteoclast differentiation and function have not been fully elucidated. In this study, we found that 4T1 bone metastatic mouse mammary tumor cell-derived EVs (4T1-EVs) are taken up by mouse bone marrow macrophages to facilitate osteoclastogenesis. Furthermore, treatment of mature osteoclasts with 4T1-EVs promoted bone resorption, which was accompanied by enhanced survival of mature osteoclasts through the negative regulation of Caspase-3. By comparing the miRNA content in 4T1-EVs with that in 67NR non-metastatic mouse mammary tumor cell-derived EVs (67NR-EVs), miR-92a-3p was identified as one of the most enriched miRNAs in 4T1-EVs, and its transfer into mature osteoclasts significantly reduced apoptosis. Bioinformatic and western blot analyses revealed that miR-92a-3p directly targeted phosphatase and tensin homolog (PTEN) in mature osteoclasts, resulting in increased levels of phospho-Akt. Our findings provide novel insights into the EV-mediated regulation of osteoclast survival through the transfer of miR-92a-3p, which enhances mature osteoclast survival via the Akt survival signaling pathway, thus promoting bone resorption. 抄録：英語フィールド
Author：*Norihisa Uehara, Yukari Kyumoto-Nakamura, Yoshikazu Mikami, Manabu Hayatsu, Soichiro Sonoda, Takayoshi Yamaza, Akiko Kukita, Toshio KukitaTitle：miR-92a-3p encapsulated in bone metastatic mammary tumor cell-derived extracellular vesicles modulates mature osteoclast longevity Announcement information:Cancer Sci Vol: 113 Issue: 12 Page: 4219-4229Keyword：apoptosis; breast cancer; extracellular vesicles; miRNA; osteoclastAn abstract：Aberrant osteoclast formation and activation are the hallmarks of osteolytic metastasis. Extracellular vesicles (EVs), released from bone metastatic tumor cells, play a pivotal role in the progression of osteolytic lesions. However, the mechanisms through which tumor cell-derived EVs regulate osteoclast differentiation and function have not been fully elucidated. In this study, we found that 4T1 bone metastatic mouse mammary tumor cell-derived EVs (4T1-EVs) are taken up by mouse bone marrow macrophages to facilitate osteoclastogenesis. Furthermore, treatment of mature osteoclasts with 4T1-EVs promoted bone resorption, which was accompanied by enhanced survival of mature osteoclasts through the negative regulation of Caspase-3. By comparing the miRNA content in 4T1-EVs with that in 67NR non-metastatic mouse mammary tumor cell-derived EVs (67NR-EVs), miR-92a-3p was identified as one of the most enriched miRNAs in 4T1-EVs, and its transfer into mature osteoclasts significantly reduced apoptosis. Bioinformatic and western blot analyses revealed that miR-92a-3p directly targeted phosphatase and tensin homolog (PTEN) in mature osteoclasts, resulting in increased levels of phospho-Akt. Our findings provide novel insights into the EV-mediated regulation of osteoclast survival through the transfer of miR-92a-3p, which enhances mature osteoclast survival via the Akt survival signaling pathway, thus promoting bone resorption. 