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Disruption by SaCas9 Endonuclease of HERV-Kenv, a Retroviral Gene with Oncogenic and Neuropathogenic Potential, Inhibits Molecules Involved in Cancer and Amyotrophic Lateral Sclerosis.
Ibba, Gabriele; Piu, Claudia; Uleri, Elena; Serra, Caterina; Dolei, Antonina.
Afiliación
  • Ibba G; Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43B, 07100 Sassari, Italy. g.ibba@gmx.com.
  • Piu C; Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43B, 07100 Sassari, Italy. claudia-piu@tiscali.it.
  • Uleri E; Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43B, 07100 Sassari, Italy. elenauleri@tiscali.it.
  • Serra C; Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43B, 07100 Sassari, Italy. cserra@uniss.it.
  • Dolei A; Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43B, 07100 Sassari, Italy. doleivir@uniss.it.
Viruses ; 10(8)2018 08 07.
Article en En | MEDLINE | ID: mdl-30087231
The human endogenous retrovirus (HERV)-K, human mouse mammary tumor virus like-2 (HML-2) subgroup of HERVs is activated in several tumors and has been related to prostate cancer progression and motor neuron diseases. The cellular splicing factor 2/alternative splicing factor (SF2/ASF) is a positive regulator of gene expression, coded by a potent proto-oncogene, amplified, and abnormally expressed in tumors. TAR DNA-binding protein-43 (TDP-43) is a DNA/RNA-binding protein, negative regulator of alternative splicing, known for causing neurodegeneration, and with complex roles in oncogenesis. We used the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology, with the Cas9 system from Staphylococcus aureus (SaCas9), to disrupt the HERV-K(HML-2)env gene, and evaluated the effects on cultured cells. The tool was tested on human prostate cancer LNCaP cells, whose HERV-Kenv transcription profile is known. It caused HERV-K(HML-2)env disruption (the first reported of a HERV gene), as evaluated by DNA sequencing, and inhibition of env transcripts and proteins. The HERV-K(HML-2)env disruption was found to interfere with important regulators of cell expression and proliferation, involved in manaling, RNA-binding, and alternative splicing, such as epidermal growth factor receptor (EGF-R), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), SF2/ASF, and TDP-43. These novel findings suggest that HERV-K is not an innocent bystander, they reinforce its links to oncogenesis and motor neuron diseases, and they open potential innovative therapeutic options.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oncogenes / Proteínas del Envoltorio Viral / Retrovirus Endógenos / Esclerosis Amiotrófica Lateral / Neoplasias Límite: Humans / Male Idioma: En Revista: Viruses Año: 2018 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oncogenes / Proteínas del Envoltorio Viral / Retrovirus Endógenos / Esclerosis Amiotrófica Lateral / Neoplasias Límite: Humans / Male Idioma: En Revista: Viruses Año: 2018 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Suiza