2. Academic Validation
  3. Small activating RNA-activated NIS gene promotes 131I uptake and inhibits thyroid cancer via AMPK/mTOR pathway

Small activating RNA-activated NIS gene promotes 131I uptake and inhibits thyroid cancer via AMPK/mTOR pathway

  • Pathol Res Pract. 2022 Jan:229:153735. doi: 10.1016/j.prp.2021.153735.
Li Jia 1,  Yan Chen 2,  Fukun Chen 2,  Juan Lv 2,  Yanling Li 2,  Fei Hou 2,  Zhixian Yang 2,  Zhiyong Deng 3
Affiliations

Affiliations

  • 1 Department of Nuclear Medicine, The Third Affiliated Hospital of Kunming Medical University, No. 519 Kunzhou Road, Kunming, Yunnan 650118, China; The Affiliated Hospital of Yunnan University, Yunnan Second People's Hospital, No.176 Qingnian Road, Kunming, Yunnan 650021, China.
  • 2 Department of Nuclear Medicine, The Third Affiliated Hospital of Kunming Medical University, No. 519 Kunzhou Road, Kunming, Yunnan 650118, China.
  • 3 Department of Nuclear Medicine, The Third Affiliated Hospital of Kunming Medical University, No. 519 Kunzhou Road, Kunming, Yunnan 650118, China. Electronic address: [email protected].
PMID: 34922208 DOI: 10.1016/j.prp.2021.153735
Abstract

Background: Sodium/iodide symporter (NIS) acts as a vital role in regulation of iodide uptake in thyroid Cancer. However, the efficient approach to increase NIS expression and the mechanism of NIS-mediated iodide uptake in thyroid Cancer remain unclear.

Methods: Small activating RNA (saRNA) was used to promote NIS expression. And the cell viability, Apoptosis, and Autophagy were detected using Cell count-kit 8 (CCK-8), Annexin V-FITC/PI double staining, and GFP-LC3 immunofluorescence assays, respectively. The protein levels of Caspase 3, Bax, Bcl-2, ATG5, ATG12, LC3B Ⅱ to LC3B Ⅰ, Beclin 1, p62, AMPK, mTOR, p70S6K, actin, and phosphorylation of AMPK, mTOR, p70S6K were determined by western blotting. Moreover, a nude murine node with transplanted NC-dsRNA or NIS-482-transfected SW579 cells was used to examine the effect of NIS-mediated Autophagy in vivo. And the levels of Caspase 3 and ki67 were examined by immunohistochemical staining assay.

Results: saRNA mediated NIS mRNA and protein upregulated in SW579 cells. saRNA-mediated NIS expression inhibited cell proliferation, induced Apoptosis and Autophagy, and promoted iodide uptake in SW579 cells. Moreover, the effects of NIS on cells were enhanced by Autophagy activator Rapamycin whereas reversed by Autophagy inhibitor 3-Methyladenine (3-MA). For mechanism analysis, we found that NIS upregulation exerted the effects on cell proliferation, Apoptosis, Autophagy, and iodide uptake via regulating AMPK/mTOR pathway. We also demonstrated that saRNA-mediated NIS expression promoted iodide uptake in vivo.

Conclusion: saRNA-mediated NIS expression acted as a critical role in increasing iodide uptake via AMPK/mTOR pathway in thyroid Cancer.

Keywords

AMPK; Autophagy; Iodide; MTOR; NIS.

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