Reduction of Tumor Growth with RNA-Targeting Treatment of the NAB2–STAT6 Fusion Transcript in Solitary Fibrous Tumor Models.
Simple Summary: Solitary fibrous tumor (SFT) is a soft-tissue sarcoma occurring in adults and infants. This nonhereditary cancer is the result of an environmental intrachromosomal gene fusion between NAB2 and STAT6 on chromosome 12. Either surgery or radiation is the first line of treatment for this...
| Publicado en: | Cancers Vol. 15; no. 12; pp. 3127 - 3143 |
|---|---|
| Autores principales: | , , , , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
MDPI
Jun2023
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=164614905&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 164614905 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 20726694 B74B jtl: Cancers issn: 20726694 maglogo: N pubinfo: dt: Jun2023 vid: 15 iid: 12 pid: 97109 pub: MDPI artinfo: ui: 164614905 164614905 164614905 10.3390/cancers15123127 164614905 ppf: 3127 ppct: 16 formats: tig: atl: Reduction of Tumor Growth with RNA-Targeting Treatment of the NAB2–STAT6 Fusion Transcript in Solitary Fibrous Tumor Models. aug: au: Li, Yi Nguyen, John T. Ammanamanchi, Manasvini Zhou, Zikun Harbut, Elijah F. Mondaza-Hernandez, Jose L. Meyer, Clark A. Moura, David S. Martin-Broto, Javier Hayenga, Heather N. Bleris, Leonidas affil: Department of Bioengineering, University of Texas at Dallas, Richardson, TX 75080, USA sug: subj: Sarcoma Therapy Sarcoma Familial and Genetic Disease Progression Prevention and Control RNA Therapeutic Use Transcription Factors Animal Studies Mice In Vitro Studies Cell Line, Tumor Drug Effects Tissue Engineering Cell Movement Signal Transduction Nucleotides Cell Proliferation Funding Source ab: Simple Summary: Solitary fibrous tumor (SFT) is a soft-tissue sarcoma occurring in adults and infants. This nonhereditary cancer is the result of an environmental intrachromosomal gene fusion between NAB2 and STAT6 on chromosome 12. Either surgery or radiation is the first line of treatment for this cancer; however for many, this becomes challenging, as the cancer can travel to inoperable areas or reoccur in locations already irradiated. Currently there is no approved chemotherapy regimen for SFTs. Anti-angiogenic drugs developed to treat other cancers have been used on SFTs with limited success. Therefore, there is a need for systemic therapy. In this study, we showed that RNA-targeting technologies (antisense oligonucleotides and CRISPR/CasRx) can be used to specifically suppress the expressions of NAB2–STAT6 fusion transcripts, but not wild type STAT6, and reduce cell proliferation and tumor growth. These results provide the foundation for a potentially novel therapeutical strategy for SFTs. Solitary fibrous tumor (SFT) is a rare soft-tissue sarcoma. This nonhereditary cancer is the result of an environmental intrachromosomal gene fusion between NAB2 and STAT6 on chromosome 12, which fuses the activation domain of STAT6 with the repression domain of NAB2. Currently there is not an approved chemotherapy regimen for SFTs. The best response on available pharmaceuticals is a partial response or stable disease for several months. The purpose of this study is to investigate the potential of RNA-based therapies for the treatment of SFTs. Specifically, in vitro SFT cell models were engineered to harbor the characteristic NAB2–STAT6 fusion using the CRISPR/SpCas9 system. Cell migration as well as multiple cancer-related signaling pathways were increased in the engineered cells as compared to the fusion-absent parent cells. The SFT cell models were then used for evaluating the targeting efficacies of NAB2–STAT6 fusion-specific antisense oligonucleotides (ASOs) and CRISPR/CasRx systems. Our results showed that fusion specific ASO treatments caused a 58% reduction in expression of fusion transcripts and a 22% reduction in cell proliferation after 72 h in vitro. Similarly, the AAV2-mediated CRISPR/CasRx system led to a 59% reduction in fusion transcript expressions in vitro, and a 55% reduction in xenograft growth after 29 days ex vivo. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|