Abstract
Current treatments for hepatocellular carcinoma (HCC) have shown inadequate. MicroRNA-122 (miR-122) mediated RNA interference brings new prospects. A safe, efficient miRNA delivery system is an indispensable assurance. Previously, we developed an MS2 bacteriophage virus-like particle (VLP)-based microRNA delivery system crosslinked with the HIV TAT peptide, which served as an effective inhibitor in the treatments of systemic lupus erythematosus and osteoporosis. However, defects, such as low crosslinking efficiency, high cost, and potential toxicity of the crosslinking agent, needed to be confronted. Therefore, TAT peptide was designed to display on the surface of MS2 VLPs, instead of being chemically crosslinked, using the platform of phage surface display. The results reflected that MS2 VLPs displaying TAT could effectively penetrate the cytomembrane and deliver miR-122. Additionally, its inhibitory effects on HCC were significant in Hep3B, HepG2, and Huh7 cells and Hep3B related animal models. Thus, we have established a novel miR-122 delivery system based on MS2 VLPs surface displaying TAT peptide, which could effectively perform the function of penetrating cytomembrane and the inhibition of HCC.
Highlights
Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumor, with the third most frequent cause of cancer-related deaths [1,2,3]
We developed an MS2 bacteriophage virus-like particle (VLP)-based microRNA delivery system crosslinked with the human immunodeficiency virus (HIV) TAT peptide, which served as an effective inhibitor in the treatments of systemic lupus erythematosus and osteoporosis
We have established a novel miR-122 delivery system based on MS2 VLPs surface displaying TAT peptide, which could effectively perform the function of penetrating cytomembrane and the inhibition of hepatocellular carcinoma (HCC)
Summary
Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumor, with the third most frequent cause of cancer-related deaths [1,2,3]. MRX34 as the first anticancer miRNA drug has entered Phase I clinical trials in patients with primary liver cancer and metastatic HCC [10,11,12], which suggested the prospects of applying therapeutic miRNAs to HCC. MiR-122, the downregulation of which has been identified both in patients with HCC and HCC-derived cell lines [13,14,15,16], negatively regulates several target gene expressions, such as those of cyclin G1, serum response factor (Srf), and insulin-like growth factor 1 receptor (Igf1r). The miR-122 mimetic was delivered to observe its inhibitory effects on HCC in vivo and in vitro, reflecting its potential as an anticancer miRNA drug candidate
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