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Review
. 2015 Jan;22(1):46-57.
doi: 10.1038/cdd.2014.136. Epub 2014 Sep 5.

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

E Callegari  1 , L Gramantieri  2 , M Domenicali  3 , L D'Abundo  1 , S Sabbioni  4 , M Negrini  1
Affiliations
Review

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

E Callegari et al. Cell Death Differ. 2015 Jan.

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.

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Figures

Figure 1
Figure 1
Aberrant miRNA expression in liver cancer promotes cell-cycle progression. A simplified pathway of cell cycle regulation is presented that shows the effects of various aberrantly expressed miRNAs in liver cancer. Upregulated miRNAs are indicated with a red up arrow, and downregulated miRNAs are indicated with a green down arrow. Upregulated miRNAs exert a stronger inhibitory effect on their targets, whereas downregulated miRNAs mediate weaker effects on their targets. Taken together, multiple aberrant miRNAs act on this pathway to support cell cycle progression
Figure 2
Figure 2
Aberrant miRNA expression in liver cancer affects the functionality of apoptosis pathways. A simplified apoptosis pathway is presented that shows the effects of various miRNAs that are aberrantly expressed in liver cancer. The aberrant expression of multiple miRNAs supports cell survival
Figure 3
Figure 3
Aberrant miRNA expression in liver cancer supports the activation of various signaling pathways. Simplified diagrams of RAS/MAPK, PI3K/AKT/mTOR, and WNT/β-catenin signaling pathways are shown, along with the effects of various miRNAs that are aberrantly expressed in liver cancer. As a result, cell proliferation, survival, and maintenance of stemness are enhanced
Figure 4
Figure 4
miRNA-based approaches that are moving toward clinical trials. An overview of the many preclinical studies that have produced promising results, as well as the clinical trials that are being planned or are underway
See this image and copyright information in PMC

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