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Lentivirus-mediated siRNA knockdown of SPHK1 inhibits proliferation and tumorigenesis of neuroblastoma

BACKGROUND: The overexpression of sphingosine kinase 1 (SPHK1) is responsible for the progress of many cancers. However, the role of SPHK1 in the development and progression of neuroblastoma (NB) remain largely unknown. Here in this study, we explored whether silencing SPHK1 by lentivirus-mediated s...

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Autores principales: Su, Lin, Tian, Junyan, Sun, Jinsong, Han, Nuan, Feng, Lin, Yu, Baohua, Wang, Yuepeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203087/
https://www.ncbi.nlm.nih.gov/pubmed/30425511
http://dx.doi.org/10.2147/OTT.S180962
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author Su, Lin
Tian, Junyan
Sun, Jinsong
Han, Nuan
Feng, Lin
Yu, Baohua
Wang, Yuepeng
author_facet Su, Lin
Tian, Junyan
Sun, Jinsong
Han, Nuan
Feng, Lin
Yu, Baohua
Wang, Yuepeng
author_sort Su, Lin
collection PubMed
description BACKGROUND: The overexpression of sphingosine kinase 1 (SPHK1) is responsible for the progress of many cancers. However, the role of SPHK1 in the development and progression of neuroblastoma (NB) remain largely unknown. Here in this study, we explored whether silencing SPHK1 by lentivirus-mediated siRNA could be employed as a potential therapeutic target for NB. MATERIALS AND METHODS: Lentivirus was adopted to load SPHK1 siRNA. The results were obtained using RT-qPCR, Western blot, cell proliferation assay, transwell cell migration/invasion assays as well as in vivo xenograft tumor models in nude mice. RESULTS: Our results demonstrated that SPHK1 mRNA was upregulated in SH-SY5Y and SK-N-SH cells as well as in human NB tissues. SPHK1 knockdown by siRNA resulted in impaired proliferation, increased apoptosis, as well as impaired migration and invasion of SH-SY5Y and SK-N-SH cells. In addition, the in vivo study suggested that SPHK1 knockdown significantly reduced the tumorigenesis of SH-SY5Y xenograft model. Furthermore, intratumorally administered lentivirus-SPHK1 siRNA could significantly inhibit tumor growth in an SH-SY5Y xenograft mice model. Intensive investigations on mechanism revealed that these effects were achieved through the deactivation of STAT3 pathways. CONCLUSION: These data suggest that SPHK1 inhibition via downregulation of STAT3 pathways by lentivirus-mediated siRNA knockdown can significantly suppress NB progression, which could be a promising target for future gene therapy of NB.
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spelling pubmed-62030872018-11-13 Lentivirus-mediated siRNA knockdown of SPHK1 inhibits proliferation and tumorigenesis of neuroblastoma Su, Lin Tian, Junyan Sun, Jinsong Han, Nuan Feng, Lin Yu, Baohua Wang, Yuepeng Onco Targets Ther Original Research BACKGROUND: The overexpression of sphingosine kinase 1 (SPHK1) is responsible for the progress of many cancers. However, the role of SPHK1 in the development and progression of neuroblastoma (NB) remain largely unknown. Here in this study, we explored whether silencing SPHK1 by lentivirus-mediated siRNA could be employed as a potential therapeutic target for NB. MATERIALS AND METHODS: Lentivirus was adopted to load SPHK1 siRNA. The results were obtained using RT-qPCR, Western blot, cell proliferation assay, transwell cell migration/invasion assays as well as in vivo xenograft tumor models in nude mice. RESULTS: Our results demonstrated that SPHK1 mRNA was upregulated in SH-SY5Y and SK-N-SH cells as well as in human NB tissues. SPHK1 knockdown by siRNA resulted in impaired proliferation, increased apoptosis, as well as impaired migration and invasion of SH-SY5Y and SK-N-SH cells. In addition, the in vivo study suggested that SPHK1 knockdown significantly reduced the tumorigenesis of SH-SY5Y xenograft model. Furthermore, intratumorally administered lentivirus-SPHK1 siRNA could significantly inhibit tumor growth in an SH-SY5Y xenograft mice model. Intensive investigations on mechanism revealed that these effects were achieved through the deactivation of STAT3 pathways. CONCLUSION: These data suggest that SPHK1 inhibition via downregulation of STAT3 pathways by lentivirus-mediated siRNA knockdown can significantly suppress NB progression, which could be a promising target for future gene therapy of NB. Dove Medical Press 2018-10-18 /pmc/articles/PMC6203087/ /pubmed/30425511 http://dx.doi.org/10.2147/OTT.S180962 Text en © 2018 Su et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Su, Lin
Tian, Junyan
Sun, Jinsong
Han, Nuan
Feng, Lin
Yu, Baohua
Wang, Yuepeng
Lentivirus-mediated siRNA knockdown of SPHK1 inhibits proliferation and tumorigenesis of neuroblastoma
title Lentivirus-mediated siRNA knockdown of SPHK1 inhibits proliferation and tumorigenesis of neuroblastoma
title_full Lentivirus-mediated siRNA knockdown of SPHK1 inhibits proliferation and tumorigenesis of neuroblastoma
title_fullStr Lentivirus-mediated siRNA knockdown of SPHK1 inhibits proliferation and tumorigenesis of neuroblastoma
title_full_unstemmed Lentivirus-mediated siRNA knockdown of SPHK1 inhibits proliferation and tumorigenesis of neuroblastoma
title_short Lentivirus-mediated siRNA knockdown of SPHK1 inhibits proliferation and tumorigenesis of neuroblastoma
title_sort lentivirus-mediated sirna knockdown of sphk1 inhibits proliferation and tumorigenesis of neuroblastoma
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203087/
https://www.ncbi.nlm.nih.gov/pubmed/30425511
http://dx.doi.org/10.2147/OTT.S180962
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