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. 2013 Aug;98(8):E1334-44.
doi: 10.1210/jc.2013-1053. Epub 2013 May 29.

Down-regulation of miR-218-2 and its host gene SLIT3 cooperate to promote invasion and progression of thyroid cancer

Hongyu Guan  1 , Gouhong Wei, Jueheng Wu, Donghong Fang, Zhihong Liao, Haipeng Xiao, Mengfeng Li, Yanbing Li
Affiliations

Down-regulation of miR-218-2 and its host gene SLIT3 cooperate to promote invasion and progression of thyroid cancer

Hongyu Guan et al. J Clin Endocrinol Metab. 2013 Aug.

Abstract

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.

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