Abstract
The incidence of papillary thyroid cancer (PTC) has been rapidly increasing in recent years. PTC is prone to lymph node metastasization, which further increases the recurrence rate and mortality of thyroid cancer. However, the underlying mechanisms of this process remain elusive. Several reports have shown that the microRNA miR-215 plays an important role in cancer metastasis. Here, we investigated, for the first time, the potential association between miR-215 and metastasis in PTC. The results of qPCR analysis demonstrated that miR-215 was downregulated in PTC cell lines and tissues, and lower levels of miR-215 correlated with lymph node metastasis of PTC. In vitro and in vivo assays revealed that restoration of miR-215 dramatically inhibited PTC cell proliferation and metastasis. We identified ADP ribosylation factor guanine nucleotide-exchange factor 1 (ARFGEF1) as the target, which mediated the function of miR-215. The expression of ARFGEF1 was inhibited by miR-215, and the effects of miR-215 were abrogated by re-expression of ARFGEF1. Moreover, we found that miR-215 suppressed PTC metastasis by modulating the epithelial–mesenchymal transition via the AKT/GSK-3β/Snail signaling. In summary, our study proves that miR-215 inhibits PTC proliferation and metastasis by targeting ARFGEF1 and indicates miR-215 as a biomarker for PTC prognosis.
Highlights
Thyroid cancer (TC), deriving from thyroid follicular epithelial cells or parafollicular C cells, is the most frequent malignant tumor in the endocrine system
Results miR-215 is downregulated in papillary thyroid cancer (PTC) tissues and cell lines To investigate the role of miR-215 in PTC, we performed Quantitative PCR (qPCR) assays and measured miR-215 expression in 48 paired PTC tissues and the corresponding adjacent normal tissues (ANT)
We found that miR-215 expression was significantly lower in PTC tissues than in ANT (Fig. 1a)
Summary
Thyroid cancer (TC), deriving from thyroid follicular epithelial cells or parafollicular C cells, is the most frequent malignant tumor in the endocrine system. Papillary thyroid cancer (PTC) is the most common type of TC and, in recent years, its incidence has been increasing worldwide[1]. The knowledge of the underlying mechanisms in PTC LNM is essential to make appropriate therapeutic decisions and improve the prognosis of patients with PTC. MicroRNAs (miRNAs) are short (~22 nucleotides), single-stranded RNAs that regulate gene expression at the post-transcriptional level by binding to the 3′-untranslated region (3′-UTR) of target mRNAs, leading to their degradation or inhibition of their translation[4]. Increasing evidence suggests that miRNAs are involved in various biological processes, including cell proliferation, migration, invasion, differentiation, and immune responses[5]
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