MicroRNAs in liver cancer: a model for investigating pathogenesis and novel therapeutic approaches

Abstract

MicroRNAs (miRNAs) constitute a large class of short RNAs (e.g., 20-24 nucleotides in length), whose main function is to posttranscriptionally regulate the expression of protein-coding genes. Their importance in tumorigenesis has been demonstrated over the past decade, and correspondingly, they have emerged as potential therapeutic molecules and targets. Liver cancer is one of the most common neoplastic diseases worldwide, and it currently has a poor prognosis owing to largely ineffective therapeutic options. Liver cancer is also an excellent model for testing miRNA-based therapy approaches as it can be easily targeted with the systemic delivery of oligonucleotides. In recent years, the role of miRNAs in hepatocellular carcinoma (HCC) has been established with molecular studies and the development of animal models. These studies have also provided the basis for evaluating the therapeutic potential of miRNAs, or anti-miRNAs. In general, the safety of miRNAs has been proven and antitumor activity has been observed. Moreover, because of the absence or presence of mild side effects, the prophylactic use of miRNA-based approaches may be foreseen.

Vector-Based let-7a miRNAs Function as Suppressors of Multiple Oncogenes in SK-N-MC and SHEP Neuroblastoma Cells

“…The highly conserved let-7 miRNAs have also been shown to have suppressive effects in cancers with overexpression of RAS proteins and RAS oncogenes with lesser mutations, such as hepatocellular carcinoma [4,[16][17][18]. We previously verified the presence of let-7a target wild-type RAS genes in humans through luciferase activity.…”

“…miRNAs now serve as new therapeutic molecules for the treatment of cancer. They are used to replace tumor suppressors or to silence oncogenes [4].…”

The application of antitumor drug-targeting models on liver cancer

“…Taken together, the investigation of animal models is an essential aspect of the study on antitumortargeting agents (Arap et al, 1998;Kukowska-Latallo et al, 2005). With the further studies of pharmacology, pharmacodynamics, biopharmaceutics and pharmacokinetics (Callegari et al, 2014;Denzler et al, 2014), it is expected that the research level of the antitumor-targeting models would attain a deeper level and accomplish more superior achievements (Chen & Calvisi, 2014;Verhaegh et al, 2014). …”

Emerging role of microRNAs in the treatment of hepatocellular carcinoma

“…41 MiR-141 upregulation, which has been described in hepatitis C virus-infected human hepatocytes in vitro, causes the depletion of DLC-1 protein, a tumor suppressor frequently deleted in HCC. 42 Animal models based on miRNAs have confirmed their role in tumorigenesis, both in hematopoietic diseases [43][44][45][46] and in solid tumors, such as HCC, [47][48][49] thereby allowing preclinical studies based on the inhibition or restoration of miRNA (see Callegari et al 50 for a comprehensive review, and Table 2). …”