MiR-128 suppresses the growth of thyroid carcinoma by negatively regulating SPHK1.

ABSTRACT

Accumulating evidences have emphasized the essential roles of differentially expressed miRNAs in papillary thyroid cancer (PTC) and follicular thyroid carcinoma (FTC) progression. MiR-128 has been reported to be down-regulated in multiple cancers to restrain tumor growth. However, the role of miR-128 in the development of PTC and FTC and the underlying mechanism remain to be unclear. In this present study, the results indicated that miR-128 expression was markedly down-regulated in PTC and FTC tissues and various thyroid carcinoma cell lines. Functional analysis indicated that over-expression of miR-128 suppressed PTC and FTC cancer cell growth, induced apoptosis and cell cycle arrest in G0/G1 phase. In addition, miR-128 over-expression markedly inhibited cancer cell migration and invasion. However, the processes above were reversed by silencing miR-128 expressions in thyroid tumor cells. Following, we characterized sphingosine kinase-1 (SPHK1) as a direct target of miR-128 that interacted with the 3'-untranslated region (UTR) of SPHK1, and the results were confirmed by using luciferase-reporter assay. We also observed that SPHK1 expression was decreased and negatively correlated with miR-128 expression in PTC and FTC tissues clinically. Importantly, ectopic expression of SPHK1 significantly abrogated the tumor-suppressive effect induced by miR-128, as supported by the reduced apoptosis, while the enhanced proliferation and metastasis. Finally, over-expressing miR-128 apparently reduced the tumor growth rate and tumor weight in vivo using xenograft tumor model, accompanied with a remarkable decrease of SPHK1. Thus, our study illustrated that miR-128 might be a tumor suppressor microRNA that played an essential role in thyroid carcinoma progression.