Abstract
Follicular thyroid carcinoma (FTC) is a more aggressive form of thyroid cancer than the common papillary type. Alpha-2,8-sialyltransferase (ST8SIA) family members are expressed in various cancers and may be associated with FTC progression. In this study, we measured ST8SIA family expression in two FTC cell lines with different invasive potentials (FTC-133 and FTC-238) and Nthy-ori 3-1 cell lines, as well as FTC and normal thyroid tissues. ST8SIA4 was downregulated in the highly invasive FTC-238 cells and FTC tissues. Additionally, ST8SIA4 inhibited proliferation, migration and invasion of FTC both in vitro and in vivo. miR-146a and miR-146b were previously shown to be upregulated in thyroid carcinoma, and bioinformatics analyses indicated that miR-146a and miR-146b inhibit ST8SIA4. We found that miR-146a and miR-146b were significantly upregulated in FTC and promoted tumour progression. Furthermore, ST8SIA4 restoration decreased the invasiveness of miR-146a/b-overexpressing FTC-133 cells, and ST8SIA4 suppression reversed the effects of miR-146a/b inhibition in FTC-238 cells. We showed that miR-146a/b activated the PI3K-AKT-mTOR signalling pathway at least partially via suppression of ST8SIA4. Thus, our results demonstrate that miR-146a and miR-146b promote proliferation, migration and invasion of FTC via inhibition of ST8SIA4.
Highlights
Thyroid cancer is the most common endocrine neoplasm; it accounts for approximately 1% of all new malignant diseases, and its annual incidence is increasing worldwide [1]
ST8SIA4 inhibited proliferation, migration and invasion of Follicular thyroid carcinoma (FTC) both in vitro and in vivo. miR-146a and miR-146b were previously shown to be upregulated in thyroid carcinoma, and bioinformatics analyses indicated that miR-146a and miR-146b inhibit ST8SIA4
No significant differences were found in the remaining ST8SIA family members in the tissue samples, whereas the expression of ST8SIA6 was significantly higher in the FTC tissues than that of the normal thyroid tissues (*p < 0.05)
Summary
Thyroid cancer is the most common endocrine neoplasm; it accounts for approximately 1% of all new malignant diseases, and its annual incidence is increasing worldwide [1]. Thyroid cancer is classified into four types: papillary (85% prevalence), follicular (10% prevalence), medullary (3–4% prevalence), and anaplastic thyroid cancer (1–2% prevalence) [2, 3]. Compared with papillary thyroid cancer (PTC), follicular thyroid cancer (FTC) is more aggressive and harder to diagnose [4]. Previous reports demonstrated that sialic acid is involved in various biological processes, including cell-cell adhesion, immune defence, tumour cell metastasis, and inflammation [7,8,9,10]. Increasing evidence has indicated that the ST8SIA family is associated with several human tumours. ST8SIA4 is involved in the development of multidrug-resistant neoplasms in acute myeloid leukaemia cells [11]. Whether the ST8SIA family has biological functions in FTC is poorly understood
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