American Association for Cancer Research
Browse
15357163mct181020-sup-208490_2_supp_5616570_ptt33m.pdf (158.32 kB)

Supplemental Figure 1 from Anti-miRNA Oligonucleotide Therapy for Chondrosarcoma

Download (158.32 kB)
journal contribution
posted on 2023-04-03, 15:22 authored by Xiaojuan Sun, Yupeng Chen, Hongchuan Yu, Jason T. Machan, Ashna Alladin, Jose Ramirez, Ross Taliano, Jesse Hart, Qian Chen, Richard M. Terek

Lung metastatic burden quantified as number of nodules per lung and area of nodules as a percent of total lung area.

Funding

National Institute of General Medical Sciences

NSF

Rhode Island Foundation

History

ARTICLE ABSTRACT

Chondrosarcoma is a highly aggressive primary malignant bone tumor mostly occurring in adults. There are no effective systemic treatments, and patients with this disease have poor survival. miR-181a is an oncomiR that is overexpressed in high-grade chondrosarcoma and promotes tumor progression. Regulator of G-protein signaling 16 (RGS16) is a target of miR-181a. Inhibition of RGS16 expression by miR-181a enhances CXC chemokine receptor 4 signaling, which in turn increases MMP1 and VEGF expression, angiogenesis, and metastasis. Here, we report the results of systemic treatment with anti-miRNA oligonucleotides (AMO) directed against miR-181a utilizing a nanopiece delivery platform (NPs). NPs were combined with a molecular beacon or anti–miR-181a oligonucleotides and are shown to transfect chondrosarcoma cells in vitro and in vivo. Intratumoral injection and systemic delivery had similar effects on miR-181a expression in nude mice bearing chondrosarcoma xenografts. Systemic delivery of NPs carrying anti–miR-181a also restored RGS16 expression, decreased expression of VEGF and MMP1, MMP activity, and tumor volume by 32% at day 38, and prolonged survival from 23% to 45%. In conclusion, these data support that systemic delivery of AMO shows promise for chondrosarcoma treatment.

Usage metrics

    Molecular Cancer Therapeutics

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC