Small activating RNA upregulates NIS expression: promising potential for hepatocellular carcinoma endoradiotherapy.
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 of125I 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 after131I treatment. Meanwhile, the apoptosis of saRNA-482-transfected HepG2 and Hep3B cells significantly increased after131I treatment. The results suggest that RNA activation-mediated upregulation of NIS may have an endoradiotherapeutic potential in the treatment of HCC.
Department of Nuclear Medicine, Shanghai Seventh People's Hospital, Shanghai, China.
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W
Xia
Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Shanghai, China.
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D
Li
Department of Nuclear Medicine, Shanghai Seventh People's Hospital, Shanghai, China.
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G
Wang
Department of Nuclear Medicine, Shanghai Seventh People's Hospital, Shanghai, China.
J
J
Ni
Department of Nuclear Medicine, Shanghai Seventh People's Hospital, Shanghai, China.
J
J
Zhuang
Department of Infectious Diseases, Shanghai Seventh People's Hospital, Shanghai, China.
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M
Ha
President's Office of Shanghai Seventh People's Hospital, Shanghai, China.
J
J
Wang
Central Laboratory, Shanghai Seventh People's Hospital, Shanghai, China.
Y
Y
Ye
D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000532:radiotherapy*; D002470:Cell Survival; D018899:CpG Islands; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D009336:Necrosis; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012330:RNA, Double-Stranded / Q000235:genetics*; D027981:Symporters / Q000378:metabolism*; D015854:Up-Regulation; D000099209:Sodium-Iodide Symporters
D012330:RNA, Double-Stranded; D027981:Symporters; D000099209:Sodium-Iodide Symporters