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

Authors Su L, Tian J, Sun J, Han N, Feng L, Yu B, Wang Y

Received 20 July 2018

Accepted for publication 19 September 2018

Published 18 October 2018 Volume 2018:11 Pages 7187—7196


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Faris Farassati

Lin Su, Junyan Tian, Jinsong Sun, Nuan Han, Lin Feng, Baohua Yu, Yuepeng Wang

Department of Pediatric Surgery, Affiliated Hospital of Jining Medical University, Jining City 272029, Shandong Province, People’s Republic of China

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.

Keywords: lentivirus, siRNA, SPHK1, STAT3, neuroblastoma

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