Research Paper Volume 13, Issue 3 pp 3726—3741
SphK1-targeted miR-6784 inhibits functions of skin squamous cell carcinoma cells
- 1 Department of Plastic and Burn Surgery, The Second Affiliated Hospital of Nantong University, Nantong, China
- 2 Department of Dermatology, The Second Affiliated Hospital of Soochow University, Suzhou, China
- 3 ENT Department, The Second Affiliated Hospital of Nantong University, Nantong, China
- 4 Clinical Laboratory, The Second Affiliated Hospital of Nantong University, Nantong, China
Received: September 8, 2020 Accepted: November 3, 2020 Published: January 19, 2021
https://doi.org/10.18632/aging.202336How to Cite
Copyright: © 2021 Gong 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.
Abstract
Sphingosine kinase 1 (SphK1) is overexpressed in skin squamous cell carcinoma (SCC). It has emerged as a novel therapeutic oncotarget. The current study identified a novel SphK1-targeting microRNA, microRNA-6784 (miR-6784). Here, we show that miR-6784 is located at the cytoplasm of A431 skin SCC cells. It directly binds to SphK1 mRNA. Ectopic overexpression of miR-6784 inhibited SphK1 3’-untranslated region (UTR) luciferase activity and downregulated its expression. Moreover, miR-6784 overexpression caused ceramide accumulation in skin SCC cells. Functional studies in established (A431 and SCC9) and primary skin SCC cells revealed that miR-6784 overexpression inhibited cell viability, proliferation, migration, and invasion. It also simultaneously provoked apoptosis activation. Conversely, miR-6784 silencing by antagomiR-6784 induced SphK1 elevation and augmented A431 cell proliferation, migration, and invasion. miR-6784 overexpression-induced anti-A431 cell activity was inhibited by the expression of an UTR-null SphK1 construct. CRISPR/Cas9-induced SphK1 knockout inhibited A431 cell growth. Importantly, miR-6784 was completely ineffective when treating SphK1-knockout A431 cells. Collectively, miR-6784 silences SphK1 and inhibits skin SCC cell progression.