Sphingosine-1-phosphate induces the migration of thyroid follicular carcinoma cells through the microRNA-17/PTK6/ERK1/2 pathway

PloS One
Shitao Zhao, Jincheng Li

Abstract

Sphingosine-1-phosphate (S1P) is a bioactive lipid known to play a role in tumorigenesis and cancer progression. However, the molecular mechanisms of S1P regulated migration of papillary thyroid cancer cells are still unknown. In this study, we showed that S1P induced PTK6 mRNA and protein expression in two thyroid follicular cancer cell lines (ML-1 and FTC-133). Further studies demonstrated that induced PTK6 and its downstream signal component (ERK1/2) are involved in S1P-induced migration. Upon investigating the mechanisms behind this event, we found that miR-17 inhibited the expression of PTK6 through direct binding to its 3'-UTR. Through overexpression and knockdown studies, we found that miR-17 can significantly inhibit S1P-induced migration in thyroid follicular cancer cells. Interestingly, overexpression or knockdown of PTK6 or ERK1/2 effectively removed the inhibition of S1P-induced migration by miR-17. Furthermore, we showed that S1P decreased miR-17 expression levels. Meanwhile, in papillary thyroid cancers, miR-17 is downregulated and negatively associated with clinical staging, whereas PTK6 is upregulated and positively associated with clinical stages. Collectively, our work defines a novel signaling pathway implica...Continue Reading

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Citations

Dec 2, 2015·Biochemical and Biophysical Research Communications·Dewang FuHuamao Jiang
Dec 24, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Yingwei LuoWeifeng Sun

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Methods Mentioned

BETA
FCS
PCR
antisense oligonucleotide
transfection

Software Mentioned

miR Walk
Target Scan

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