J Cancer 2017; 8(18):3903-3915. doi:10.7150/jca.20958

Research Paper

Effects of Triple Effective RNA (teRNA) on the Inhibition of Hepatocellular Carcinoma Cells

Yuwen Xue1*, Tiejun Li2, 3*, Shuyan Liu1*, York Yuanyuan Zhu2, 3, Guilan Wang1, Luyu Fu1, Li Chen1✉

1. Department of Pathological Anatomy, Nantong University, Nantong, China;
2. Small RNA Technology and Application Institute, Nantong University, Nantong, China;
3. Biomics Biotechnologies Co., Ltd., Nantong, China.
* These authors contributed equally.

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Xue Y, Li T, Liu S, Zhu YY, Wang G, Fu L, Chen L. Effects of Triple Effective RNA (teRNA) on the Inhibition of Hepatocellular Carcinoma Cells. J Cancer 2017; 8(18):3903-3915. doi:10.7150/jca.20958. Available from http://www.jcancer.org/v08p3903.htm

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The occurrence and development of hepatocellular carcinoma (HCC) is a complicate process involved in genetic mutation and epigenetic regulation. Successful HCC therapy needs multi-targets be involved. The aim of this study was to provide a triple effective RNA (teRNA) which composed of the specific siRNAs targeting NET-1 and VEGF and dsRNA activating TLR3, and explored its anti-HCC roles and mechanism. Real-time quantitative PCR (RT-qPCR), Western blot, immunofluorescence staining, MTT, Annexin V-FITC flow cytometry, Transwell and in-vitro Angiogenesis assay were used to measure the cell biological functions and protein expression analysis. Furthermore in in-vivo mouse model, teRNA inhibited tumor growth were detected by immunohistochemistry and TUNEL assay. Results showed that the proliferation, migration and angiogenesis of HCC cells were inhibited by teRNA effectively, the cell apoptosis also was induced, and further tumor growth was suppressed in-vivo. The gene silencing mechanism of teRNA was in an Ago2-dependent manner with no interferon response. The study suggests that NET-1, VEGF and TLR3 might be better targets for HCC treatment and combined these targets in form of a multi-target small RNA, teRNA could be a stagey for the development of anti-HCC drugs.

Keywords: hepatocellular carcinoma, VEGF, NET-1, TLR3, siRNA, sliRNA, teRNA.