MicroRNA-155 contributes to plexiform neurofibroma growth downstream of MEK
| Autor: | Robert A. Coover, Jonathan Rose, Youjin Na, Jianqiang Wu, Subbaya Subramanian, Eva Dombi, Mi-Ok Kim, Liang Hu, Ashley Hall, Adam Miller, Robert F. Hennigan, Nancy Ratner, Kwangmin Choi |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Microarray Carcinogenesis Biology medicine.disease_cause Article 03 medical and health sciences Mice 0302 clinical medicine In vivo Plexiform neurofibroma Cell Line Tumor microRNA Genetics medicine Neurofibroma Animals Humans Molecular Biology Cell Proliferation Mice Knockout Mitogen-Activated Protein Kinase Kinases Neurofibromin 1 medicine.disease In vitro MicroRNAs 030104 developmental biology Cell culture 030220 oncology & carcinogenesis Cancer research Schwann Cells |
| Zdroj: | Oncogene |
| ISSN: | 1476-5594 |
| Popis: | MicroRNAs (miRs) are small non-coding RNAs that can have large impacts on oncogenic pathways. Possible functions of dysregulated miRs have not been studied in neurofibromatosis type 1 (NF1) plexiform neurofibromas (PNFs). In PNFs, Schwann cells (SCs) have biallelic NF1 mutations necessary for tumorigenesis. We analyzed a miR microarray comparing with normal and PNF SCs and identified differences in miR expression, and we validated in mouse PNFs versus normal mouse SCs by qRT-PCR. Among these, miR-155 was a top overexpressed miR, and its expression was regulated by RAS/MAPK signaling. Overexpression of miR-155 increased mature Nf1-/- mouse SC proliferation. In SC precursors, which model tumor-initiating cells, pharmacological and genetic inhibition of miR-155 decreased PNF-derived sphere numbers in vitro, and we identified Maf as a miR-155 target. In vivo, global deletion of miR-155 significantly decreased tumor number and volume, increasing mouse survival. Fluorescent nanoparticles entered PNFs, suggesting that an anti-miR might have therapeutic potential. However, treatment of established PNFs using anti-miR-155 peptide nucleic acid-loaded nanoparticles marginally decreased tumor numbers and did not reduce tumor growth. These results suggest that miR-155 plays a functional role in PNF growth and/or SC proliferation, and that targeting neurofibroma miRs is feasible, and might provide novel therapeutic opportunities. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink