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miR-29a suppresses growth and metastasis in papillary thyroid carcinoma by targeting AKT3

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Tumor Biology

Abstract

MicroRNA-29a (miR-29a) has been reported to play important roles in tumor initiation, development, and metastasis in various cancers. However, the biological function and potential mechanisms of miR-29a in papillary thyroid carcinoma (PTC) remain unclear. In the present study, we discovered that miR-29a was frequently downregulated in PTC tissues, and its expression was significantly associated with tumor size, TNM stage, and lymph node metastasis. Functional assays showed that overexpression of miR-29a markedly suppressed PTC cell proliferation, migration, and invasion and promoted PTC apoptosis and cell cycle arrest at G0/G1 phase. In vivo, miR-29a overexpression decreased tumor growth in a xenograft mouse model. Luciferase reporter assay showed that miR-29a can directly bind to the 3′ untranslated region (UTR) of AKT3 in PTC cells. Overexpreesion of miR‑29a obviously decreased AKT3 expression, thereby suppressing phosphatidylinositol 3-kinase (PI3K)/AKT pathway activation. We also confirmed that AKT3 expression was increased in PTC tissue and was inversely correlated miR-29a expression in PTC tissues. In addition, downregulation of AKT3 by siRNA mimicked the effects of miR-29a overexpression, and upregulation of AKT3 partially reversed the inhibitory effects of miR-29a. These results suggested that miR-29a could act as a tumor suppressor in PTC by targeting AKT3 and that miR-29a may potentially serve as an anti-tumor agent in the treatment of PTC.

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Authors and Affiliations

  1. Institute of Virology and AIDS Research, The First Hospital of Jilin University, Changchun, 130021, China

    Rui Li & Xiaofang Yu

  2. Department of Thyroid Surgery, The First Hospital of Jilin University, Changchun, 130021, China

    Jia Liu, Qun Li & Guang Chen

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  1. Rui Li
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  2. Jia Liu
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  3. Qun Li
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  4. Guang Chen
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  5. Xiaofang Yu
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Correspondence to Guang Chen or Xiaofang Yu.

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Guang Chen and Xiaofang Yu contributed equally to this paper.

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Li, R., Liu, J., Li, Q. et al. miR-29a suppresses growth and metastasis in papillary thyroid carcinoma by targeting AKT3. Tumor Biol. 37, 3987–3996 (2016). https://doi.org/10.1007/s13277-015-4165-9

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  • DOI: https://doi.org/10.1007/s13277-015-4165-9

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