LncRNA H19 Suppresses Metastasis of Follicular Thyroid Carcinoma via the IGF1/JAK/STAT Pathway

Long noncoding RNAs (lncRNAs), which are important functional regulators in cancer, have emerged as critical molecular regulators in various biological processes. However, the mechanisms by which H19 modulates follicular thyroid cancer (FTC) development remain largely unknown. Here, we found that the H19 expression level was lower in tumour tissues than in adjacent normal tissues of FTC patients by using next-generation sequencing technology. The results of functional experiments showed that overexpression of H19 inhibited the proliferation, migration, invasion and angiogenic ability of FTC cells. By using Gene Ontology (GO) and KEGG pathway enrichment analyses, we found that the IGF1 signalling pathway was one of the most enriched pathways within the set of upregulated mRNAs, suggesting that it may be involved in the pathogenesis and development of FTC. In this mechanism, H19 recruited the transcription factor Pax5 to the promoter region of suppressors of cytokine signalling 3 (SOCS3), which activated SOCS3 transcription. Moreover, H19 functioned as a competing endogenous RNA (ceRNA) acting as a sponge for miR-29-3p, which activated IGF2BP1. Collectively, these data indicate that H19 is a tumour suppressor in the development of FTC and that it may contribute to the improvement of FTC diagnosis and therapy. Funding Statement: This work was supported by the grants from the Science Research Project of the Department of Education of Liaoning Province (No. L2016011) and the Doctoral Scientific Research Fund of the Second Hospital of Dalian Medical University (DY2YBSQD201501). Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: Samples were obtained from patients who provided informed consent, in accordance with the ethical standards of the Second Hospital of Dalian Medical University (Dalian, China). All of the animal experiments were approved by the responsible governmental animal ethics committee and complied with the ARRIVE guidelines.