Down-Regulation of miR-218-2 and Its Host Gene SLIT3 Cooperate to Promote Invasion and Progression of Thyroid Cancer

Context: The functional relationships between intronic microRNAs (miRNAs) and their host genes in thyroid cancer remain unclear. miR-218, a miRNA down-regulated in several kinds of cancers and associated with multiple cancer phenotypes, is transcribed from 2 loci located on chromosomes 4p15.31 (miR-218-1) and 5q35.1 (miR-218-2) within the introns of SLIT2 and SLIT3, respectively. Objective: The aim of our work was to investigate the expression and the roles of miR-218-1 and miR-218-2, as well as their host genes SLIT2 and SLIT3 in thyroid carcinogenesis. Design: The expression of miR-218-1 and miR-218-2, as well as their host genes SLIT2 and SLIT3, in a panel of normal and neoplastic human thyroid tissues was assessed by quantitative RT-PCR. We restored the expression of miR-218-2 and SLIT3 in thyroid cancer cells and evaluated their effects on cell invasion, migration, and proliferation. Results: We found that miR-218-2 and its host gene SLIT3 were down-regulated concomitantly in thyroid cancer. Synergistic inhibitory effects of miR-218-2 with SLIT3 on thyroid cancer cell invasion, migration, and proliferation were observed. Moreover, the effects of miR-218-2 on thyroid cancer cells were due, at least partially, to targeting PDGFRA and PLCG1. Conclusions: These results implicate the involvement of miR-218-2 and its host gene SLIT3 in thyroid cancer cell invasion, migration, and proliferation. Our findings highlight the functional associations of intronic miRNAs and their host genes in thyroid carcinogenesis.