JCEM：miR-218-2和其宿主基因SLIT3参与甲状腺癌的发生

在甲状腺癌，内含子miRNAs与其宿主基因功能关系仍不清楚。MiR-218，一种在数种癌症中下调的miRNA，与多种癌症的表型有关，分别从位于SLIT2和SLIT3内含子内的染色体4p15.31(miR-218-1)和5q35.1(miR-218-2)上的两个位点转录。为了探讨miR-218-1和miR-218-2，以及他们的宿主基因SLIT2和SLIT3在甲状腺癌发生中的表达和作用，来自中山大学附属第一医院的李延兵教授及其团队进行了一项研究（Down-regulation of miR-218-2 and its host gene SLIT3 cooperate to promote invasion and progression of thyroid cancer），该研究发现miR-218-2和其宿主基因SLIT3参与甲状腺癌细胞侵袭、转移和增殖。这个研究结果突出了内含子miRNAs与其宿主基因在甲状腺癌发生中的功能关系。

该研究中，通过定量RT-PCR评估miR-218-1和miR-218-2，以及他们的宿主基因SLIT2和SLIT3在正常和肿瘤的人类甲状腺组织中的表达。重建甲状腺癌细胞中miR-218-2和SLIT3的表达，并评估他们在细胞侵袭、转移和增殖中的作用。

该研究结果表明，该研究发现在甲状腺癌中伴随着miR-218-2和其宿主基因SLIT3的下调。观察到miR-218-2与SLIT3在甲状腺癌细胞侵袭、转移和增殖中发挥协同抑制作用。此外，miR-218-2在甲状腺癌细胞中的作用至少部分是由于作用于PDGFRA和PLCG1。

该研究暗示miR-218-2和其宿主基因SLIT3参与甲状腺癌细胞侵袭、转移和增殖。这个研究结果突出了内含子miRNAs与其宿主基因在甲状腺癌发生中的功能关系。

Down-regulation of miR-218-2 and its host gene SLIT3 cooperate to promote invasion and progression of thyroid cancer.
Abstract
Context:The functional relationships between intronic 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 two 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 to, at least partially, targeting PDGFRA and PLCG1.Conclusions:These results implicate the involvement of miR-218-2 and its host genes 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.