Comprehensive gene and microRNA expression profiling reveals a role for miRNAs in the oncogenic roles of SphK1 in papillary thyroid cancer

Purpose The oncogenic roles of sphingosine kinase 1 (SphK1) in various cancers, including thyroid cancer, have been well demonstrated. However, the microRNAs (miRNAs) associated with the oncogenic roles of SphK1 remain largely unknown. Methods Global gene and miRNA expression in TPC1-Vector and TPC1...

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Published in:Journal of cancer research and clinical oncology 2017-04, Vol.143 (4), p.601-611
Main Authors: Liang, Weiwei, Xie, Zhiwei, Cui, Weiling, Guo, Yan, Xu, Lijuan, Wu, Jueheng, Guan, Hongyu
Format: Article
Language:English
Subjects:
Cancer Research
Carcinoma - genetics
Carcinoma, Papillary
Cellular biology
Gene expression
Gene Expression Profiling
Hematology
Humans
Internal Medicine
Kinases
Medicine
Medicine & Public Health
MicroRNAs
MicroRNAs - genetics
Oncogenes
Oncology
Original Article – Cancer Research
Phosphotransferases (Alcohol Group Acceptor) - genetics
Thyroid cancer
Thyroid Cancer, Papillary
Thyroid Neoplasms - genetics
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Summary:Purpose The oncogenic roles of sphingosine kinase 1 (SphK1) in various cancers, including thyroid cancer, have been well demonstrated. However, the microRNAs (miRNAs) associated with the oncogenic roles of SphK1 remain largely unknown. Methods Global gene and miRNA expression in TPC1-Vector and TPC1-SphK1 cells was analyzed using digital gene expression (DGE) analysis and small RNA-seq, respectively. miRNA–mRNA interactions were explored by microT-CDS, and the predicted networks were visualized using CytoScape ® . Cell invasion and migration were assessed by performing Transwell invasion and wound-healing assays. Luciferase reporter and immunoblot assays were used to evaluate the targeting of fibronectin 1 (FN1) by miR-144-3p. Results In this study, we found that overexpression of SphK1 differentially regulates the expression of 46 miRNAs and 506 mRNAs in papillary thyroid cancer (PTC) TPC1 cells. Combining bioinformatics predictions of mRNA targets with DGE data on mRNA expression allowed us to identify the mRNA targets of deregulated miRNAs. The direct interaction between miR-144-3p and FN1, which mediates the pro-invasive role of SphK1 in PTC cells, was experimentally validated. Conclusions Our results demonstrated that SphK1 overexpression drives a regulatory network governing miRNA and mRNA expression in PTC cells. We also demonstrated the roles played by miR-144-3p and FN1 in mediating the oncogenic function of SphK1, which enhanced the understanding of the etiology of PTC.
ISSN:0171-5216
1432-1335
DOI:10.1007/s00432-016-2315-0