Identifying the physiological role of cancer-secreted microRNAs in bone metastasis microenvironment

• Project/Area Number: 26893068
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Orthopaedic surgery
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Sato Shingo 東京医科歯科大学, 医歯(薬)学総合研究科, 講師 (40462220)
• Research Collaborator: TAKEDA Shu 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (30376727) ; SUNAMURA Satoko 東京医科歯科大学, 大学院医歯学総合研究科, 特任助教 (20570386)
• Project Period (FY): 2014-08-29 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 骨転移 / マイクロNRA / がん微小環境 / 骨代謝 / マイクロRNA / マイクロＲＮＡ

Outline of Final Research Achievements

A microRNA (miRNA) is a small non-cording RNA molecule that regulates gene expression. It has been recently revealed that miRNAs are delivered via exosomes from cells to cells as an intercellular communication tool. This finding suggests that, in bone metastasis microenvironment, miRNAs secreted from cancer cells act on the surrounding osteoblasts or osteoclasts, resulting in the formation of osteoblastic or osteolytic bone lesions.
In this study, based on miRNA expression analysis we identified several miRNAs that are significantly secreted from various cancer cell lines with the ability to metastasize to bone. In addition, we found that miR-X, which is markedly secreted from prostate cancer cells that cause osteoblastic lesions, remarkably promoted osteoblast differentiation via targeting two genes. Furthermore, breast cancer cells that cause osteolytic lesions were transfected with miR-X and implanted into immune-deficient mice. Interestingly, osteoblastic bone lesions were induced.

Research Products

• [Journal Article] Circadian Clock Regulates Bone Resorption in Mice. Circadian Clock Regulates Bone Resorption in Mice. (2016)
  • Author(s): Xu C, Ochi H, Fukuda T, Sato S, Sunamura S, Takarada T, Hinoi E, Okawa A, Takeda S.
  • Journal Title: J Bone Miner Res. Volume: - Issue: 7 Pages: 1344-1355
  • DOI: 10.1002/jbmr.2803
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Identification of CD146 as a marker enriched for tumor-propagating capacity reveals targetable pathways in primary human sarcoma. (2015)
  • Author(s): Wei Q, Tang YJ, Voisin V, Sato S, Hirata M, Whetstone H, Han I, Ailles L, Bader GD, Wunder J, Alman BA.
  • Journal Title: Oncotarget Volume: 6 Issue: 37 Pages: 40283-94
  • DOI: 10.18632/oncotarget.5375
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mutant IDH is sufficient to initiate enchondromatosis in mice (2015)
  • Author(s): Hirata M, Sasaki M, Cairns RA, Inoue S, Puviindran V, Li WY, Snow BE, Jones LD, Wei Q, Sato S, Tang YJ, Nadesan P, Rockel J, Whetstone H, Poon R, Weng A, Gross S, Straley K, Gliser C, Xu Y, Wunder J, Mak TW, Alman BA
  • Journal Title: Proc Natl Acad Sci USA Volume: 112(9) Issue: 9 Pages: 2829-2834
  • DOI: 10.1073/pnas.1424400112
  • Peer Reviewed / Int'l Joint Research