Research Paper Volume 12, Issue 6 pp 5399—5410
The therapeutic value of the SphK1-targeting microRNA-3677 in human osteosarcoma cells
- 1 Department of Orthopedics, Nanjing Drum Tower Hospital of Nanjing Medical University, Nanjing, China
- 2 Department of Orthopedics, Affiliated Hospital of Nanjing University of TCM, Jiangsu Province Hospital of TCM, Nanjing, China
- 3 Department of Orthopedics, Taizhou Municipal Hospital, Taizhou, China
- 4 Department of Orthopedics, The Affiliated Jiangyin Hospital of Medical College of Southeast University, Jiangyin, China
- 5 Department of Orthopedics, Children’s Hospital of Nanjing Medical University, Nanjing, China
- 6 Department of Radiotherapy and Oncology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, China
received: January 14, 2020 ; accepted: February 20, 2020 ; published: March 23, 2020 ;https://doi.org/10.18632/aging.102961
How to Cite
Copyright © 2020 Yao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Sphingosine kinase 1 (SphK1) is a potential therapeutic target for human osteosarcoma (OS). SphK1-targeting microRNAs (miRNAs) could have important therapeutic value for OS. We discovered that micorRNA-3677 (miR-3677) is a SphK1-targeting miRNA, inhibiting OS cell progression. The results of RNA-Pull down assay confirmed direct binding between biotinylated-miR-3677 and SphK1 mRNA in primary human OS cells. In established and primary human OS cells forced overexpression of miR-3677, by a lentiviral construct, decreased SphK1 3’-UTR (untranslated region) activity and downregulated SphK1 expression. Both were however enhanced with miR-3677 inhibition in OS cells. Function studies demonstrated that OS cell growth, proliferation and migration were inhibited with miR-3677 overexpression, but augmented with miR-3677 inhibition. MiR-3677 overexpression-induced anti-OS cell activity was reversed with re-expression of the 3’-UTR-depleted SphK1. Additionally, in SphK1 knockout OS cells (by CRISPR/Cas9 strategy), altering miR-3677 expression failed to further alter cell functions. Finally, we show that miR-3677 expression was significantly downregulated in primary human OS tissues, correlating with SphK1 mRNA upregulation. We conclude that targeting SphK1 by miR-3677 inhibits human OS cell progression.