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 ofI 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 I treatment. Meanwhile, the apoptosis of saRNA-482-transfected HepG2 and Hep3B cells significantly increased afterI treatment. The results suggest that RNA activation-mediated upregulation of NIS may have an endoradiotherapeutic potential in the treatment of HCC.

Reevaluation of the Effect of Iodine on Thyroid Cell Survival and Function Using PCCL3 and Nthy-ori 3-1 Cells

“…Removal of TSH for 3 days reduced 131 I uptake by approximately 50%, indicating the TSH-dependent action of iodine uptake. On the other hand, Nthy-ori 3-1 cells, irrespective of the presence or absence of TSH, showed almost negligible 131 I uptake; these low levels of iodine uptake are likely nonspecific because the similarly low levels of 131 I uptake were also observed in 8505C and HepG2 cells, both of which have been shown not to express NIS [ 29 , 30 ].…”

Network analysis reveals essential proteins that regulate sodium-iodide symporter expression in anaplastic thyroid carcinoma

“…This outcome indicates that considering all eight centrality indices explored in this study, several apoptosis-related proteins, including BCL2L1, CASP9, XIAP, CASP3, and PARP1, are important in the network. Apoptosis has been proposed as a mechanism of cell www.nature.com/scientificreports/ death after radioactive iodine uptake in thyroid 40 and non-thyroid [41][42][43][44] cancer cells. However, our results suggest that apoptosis-related proteins may have a notable role in regulating NIS expression.…”

Activating the Chromatin by Noncoding RNAs

“…Specifically, saRNA regulating cancer-related genes have reported decreased viability (55,69,105,145), inhibition of proliferation (16,156,158), invasion and/or migration of cancer cells (145,158). Alternatively, saRNA have been used to decrease resistance of cancer cells to treatment (70,157). In addition, following saRNA-mediated increase of Progesterone receptor (PR) (44), VEGF-A (34) or transcription factors (eg Krupple-like factor [KLF4] or Myc) (137,149), activation of downstream genes of the targeted gene product were also observed.…”