Small interfering RNA–mediated gene suppression as a therapeutic intervention in hepatocellular carcinoma

• Published in: Journal of cellular physiology Vol. 234; no. 4; pp. 3263 - 3276
• Main Authors: Hajiasgharzadeh, Khalil, Somi, Mohammad Hossein, Shanehbandi, Dariush, Mokhtarzadeh, Ahad, Baradaran, Behzad
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-04-2019
• Subjects: Animals; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - therapy; Chemotherapy; Drug resistance; Feasibility studies; Gene expression; Gene Expression Regulation, Neoplastic; Gene silencing; Gene therapy; Hepatocellular carcinoma; Hepatocytes; Humans; Liver; Liver cancer; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Liver Neoplasms - therapy; Nanoparticles; Neoplasia; Oligonucleotides; Ribonucleic acid; RNA; RNA interference; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; RNA-mediated interference; RNAi Therapeutics; Signal Transduction; siRNA; small interfering RNA; Treatment Outcome; gene therapy; small interfering RNA; RNA interference; hepatocellular carcinoma
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.27015

Hepatocellular carcinoma (HCC) is one of the lethal and difficult‐to‐cure cancers worldwide. Owing to the late diagnosis and drug resistance of malignant hepatocytes, treatment of this cancer by conventional chemotherapy agents is challenging, and researchers are seeking new alternative treatment options to overcome therapy resistance in this neoplasm. RNA interference (RNAi) is a potent and specific approach in targeting gene expression and has emerged as a novel therapeutic tool for many diseases, including cancers. Small interfering RNA (siRNA) is a type of RNAi that is produced intracellularly from exogenous synthetic oligonucleotides and can selectively knock down target gene expression in a sequence‐specific manner. Various factors play roles in the initiation and progression of HCC and provide multiple candidate targets for siRNA intervention. In addition, due to the liver's unique architecture and availability of some hepatic siRNA delivery methods, this organ has received much more attention as a target tissue for such oligonucleotide action. Recent advances in designing nanoparticle systems for the in vivo delivery of siRNAs have markedly enhanced the potency of siRNA‐mediated gene silencing under clinical development for HCC therapy. The utility of siRNAs as anti‐HCC agents is the subject of the current review. siRNA‐based gene therapies could be one of the main feasible approaches for HCC therapy in the future.
Upregulation of cancer‐promoting genes in hepatocellular carcinoma (HCC), which contributes to the progression of disease stages, occurs in most cases. On the contrary, siRNAs, as a novel treatment approach by the degradation of overexpressed messenger RNAs, provide therapeutic advantages for HCC patients.