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Review
. 2019 Dec 1;11(12):1906.
doi: 10.3390/cancers11121906.

MicroRNAs in Animal Models of HCC

Francesca Fornari  1   2 , Laura Gramantieri  1 , Elisa Callegari  3 , Ram C Shankaraiah  3 , Fabio Piscaglia  1   2 , Massimo Negrini  3 , Catia Giovannini  1   2
Affiliations
Review

MicroRNAs in Animal Models of HCC

Francesca Fornari et al. Cancers (Basel). .

Abstract

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality. Molecular heterogeneity and absence of biomarkers for patient allocation to the best therapeutic option contribute to poor prognosis of advanced stages. Aberrant microRNA (miRNA) expression is associated with HCC development and progression and influences drug resistance. Therefore, miRNAs have been assayed as putative biomarkers and therapeutic targets. MiRNA-based therapeutic approaches demonstrated safety profiles and antitumor efficacy in HCC animal models; nevertheless, caution should be used when transferring preclinical findings to the clinics, due to possible molecular inconsistency between animal models and the heterogeneous pattern of the human disease. In this context, models with defined genetic and molecular backgrounds might help to identify novel therapeutic options for specific HCC subgroups. In this review, we describe rodent models of HCC, emphasizing their representativeness with the human pathology and their usefulness as preclinical tools for assessing miRNA-based therapeutic strategies.

Keywords: HCC; animal models; microRNA.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
miRNA deregulated in human and rodent human hepatocellular carcinomas (HCCs) and miRNA-based approaches in preclinical models. Top panel depicts miRNA involved in human hepatocarcinogenesis from early development to advanced stages. Downregulated miRNAs are in green; upregulated miRNAs are in red. Bottom panel depicts experimental animal models of HCC and successful miRNA treatments reducing tumor burden. miRNA mimics treatments are in green; anti-miRNA (AM) treatments are in red [3,4,5,6,7,8,9,12,15,16,17,18,19,20,21,22,23,24,25,26,27].
Figure 2
Figure 2
Features of human and rat hepatocellular carcinoma. Hematoxylin-eosin staining of human (H1–H3) and rat (R1–R3) HCC showing common histopathological features. (H1–R1) Clear cell variant caused by glycogen or lipid accumulation. (H2–R2) Trabecular growth pattern. Neoplastic hepatocytes, with nuclear irregularity, are arranged in trabeculae larger than three cell plates. (H3–R3) Progression toward less-differentiated histopathological grades is marked by the appearance of irregular nuclei, nuclear, and cellular pleomorphism, frequent mitosis, and loss of trabecular or pseudoglandular structures. Original magnification 40×. Scale bars: 100 µm.
See this image and copyright information in PMC

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