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Small activating RNA upregulates NIS expression: promising potential for hepatocellular carcinoma endoradiotherapy

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Currently, the clinical strategies available for the treatment of HCC remain insufficient for the poor prognosis. Sodium/iodide symporter (NIS)-based radioiodine therapy is proposed as a promising therapeutic strategy for the treatment of HCC. However, it is difficult for HCC cells to trap iodine for the lower expression of NIS. Small activating RNA (saRNA) is a newly identified small double-stranded RNA (dsRNA) that can induce endogenous gene expression by targeting promoter sequences. Here, we designed an saRNA (saRNA-482) that targeted the NIS promoter sequences. In the cultured HepG2 cells and Hep3B cells, the expressions of NIS were upregulated after transfection of saRNA-482. In addition, the uptake of 125I increased in the cultured HepG2 and Hep3B cells transfected with saRNA-482. Furthermore, the cell viabilities were significantly inhibited in the saRNA-482-transfected HepG2 and Hep3B cells after 131I treatment. Meanwhile, the apoptosis of saRNA-482-transfected HepG2 and Hep3B cells significantly increased after 131I treatment. The results suggest that RNA activation-mediated upregulation of NIS may have an endoradiotherapeutic potential in the treatment of HCC.

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Acknowledgements

The study was supported by grants from the Natural Science Foundation of China (Nos. 81371597 and 81571718), Shanghai Municipal Commission of Health and Family Planning (Nos. 20134090 and 20124368), Key Specialty Construction Project of Pudong Health and Family Planning Commission of Shanghai (No. PWZz2013-02), Science and Technology Development Foundation of Pudong New District Science and Technology Commission (PKJ2013-Y22), Wu Jieping Medical Foundation (320.6750.14199) and Shanghai Natural Science Foundation (13ZR1431900).

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Correspondence to J Wang or Y Ye.

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Xia, W., Li, D., Wang, G. et al. Small activating RNA upregulates NIS expression: promising potential for hepatocellular carcinoma endoradiotherapy. Cancer Gene Ther 23, 333–340 (2016). https://doi.org/10.1038/cgt.2016.36

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