期刊
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
卷 107, 期 7, 页码 -出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/jnci/djv135
关键词
-
类别
资金
- Pablove Foundation
- Concern Foundation
- Saban Research Institute Research Career Development Award
- Southern California Clinical and Translational Science Institute (SC CTSI)
- Jean Perkins Foundation
- Nautica Malibu Triathlon Funds
- National Cancer Institute [P30CA014089, 5 P01 CA081403-15]
- Hugh and Audy Lou Colvin Foundation
- Shirley McKernan stewardship
- National Institutes of Health (NIH)/National Cancer Institute (NCI) [1UH2TR00943-01, 1 R01 CA182905-01]
- UT MD Anderson Cancer Center SPORE in Melanoma grant from NCI [P50 CA093459]
- Aim at Melanoma Foundation
- Miriam and Jim Mulva research funds
- Brain SPORE [2P50CA127001]
- Center for radiation Oncology Research Project
- Center for Cancer Epigenetics Pilot project
- Knowledge GAP MDACC grant
- CLL Moonshot pilot project
- UT MD Anderson Cancer Center Duncan Family Institute for Cancer Prevention and Risk Assessment
- SINF grant in colon cancer
- Laura and John Arnold Foundation
- RGK Foundation
- Estate of C. G. Johnson Jr
Background: How exosomic microRNAs (miRNAs) contribute to the development of drug resistance in the context of the tumor microenvironment has not been previously described in neuroblastoma (NBL). Methods: Coculture experiments were performed to assess exosomic transfer of miR-21 from NBL cells to human monocytes and miR-155 from human monocytes to NBL cells. Luciferase reporter assays were performed to assess miR-155 targeting of TERF1 in NBL cells. Tumor growth was measured in NBL xenografts treated with Cisplatin and peritumoral exosomic miR-155 (n = 6 mice per group) CD163, miR-155, and TERF1 levels were assessed in 20 NBL primary tissues by Human Exon Arrays and quantitative real-time polymerase chain reaction. Student's t test was used to evaluate the differences between treatment groups. All statistical tests were two-sided. Results: miR-21 mean fold change (f.c.) was 12.08+/-0.30 (P < .001) in human monocytes treated with NBL derived exosomes for 48 hours, and miR-155 mean f.c. was 4.51+/-0.25 (P < .001) in NBL cells cocultured with human monocytes for 48 hours. TERF1 mean luciferase activity in miR-155 transfected NBL cells normalized to scrambled was 0.36 +/- 0.05 (P <.001). Mean tumor volumes in Dotap-miR-155 compared with Dotap-scrambled were 322.80+/-120mm(3) and 76.00+/-39.3mm(3), P = .002 at day 24, respectively. Patients with high CD163 infiltrating NBLs had statistically significantly higher intratumoral levels of miR-155 (P = .04) and lower levels of TERF1 mRNA (P = .02). Conclusions: These data indicate a unique role of exosomic miR-21 and miR-155 in the cross-talk between NBL cells and human monocytes in the resistance to chemotherapy, through a novel exosomic miR-21/TLR8-NF-kappa B/exosomic miR-155/TERF1 signaling pathway.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据