miR-146a and miR-146b promote proliferation, migration and invasion of follicular thyroid carcinoma via inhibition of ST8SIA4
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Wei Ma1,*, Xuzi Zhao2,*, Leilei Liang1, Guangzhi Wang1, Yanyan Li3, Xiaolong Miao1, Yongfu Zhao1
1Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian 116044, Liaoning Province, China
2Hebei Medical University, Shijiazhuang 050017, Hebei Province, China
3Changping Hospital of Integrated Chinese and Western Medicine, Beijing 102200, Beijing Province, China
*These authors contributed equally to this work
Yongfu Zhao, email: email@example.com
Keywords: follicular thyroid carcinoma, ST8SIA4, miR-146a, miR-146b, invasion
Received: September 07, 2016 Accepted: February 21, 2017 Published: March 03, 2017
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.
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