Abstract
Liver cancer is a devastating cancer that ranges from relatively rare (around 2% of all cancers in the United States) to commonplace (up to 50% of cancers in underdeveloped countries). Depending upon the stage of pathogenesis, prognosis, or functional liver tissue present, transplantation or partial hepatectomy may be the only available treatment option. However, due to the rise in metabolic syndrome and the increasing demand for livers, patients often wait months or years for available organs. Due to this shortage, doctors must have other treatment options available. One promising area of cancer research lies in understanding the role of regulatory non-coding RNAs (ncRNAs) as oncogenic drivers and potential targets for prospective therapies. While the role of these ncRNAs was not initially clear, many of them have since been recognized to function as important players in the regulation of gene expression, epigenetic modification, and signal transduction in both normal and cancer cell cycles. Dysregulation of these different ncRNA subtypes has been implicated in the pathogenesis and progression of many major cancers including hepatocellular carcinoma. This review summarizes current findings on the roles noncoding RNAs play in the progression of liver cancer and the various animal models used in current research to elucidate those data.
Highlights
MiRNAs, first discovered in 1993 by Lee and colleagues in the nematode Caenorhabditis elegans [1], are a category of ncRNAs that are 19–22nt in length and that function primarily by mediating post transcriptional gene silencing
It was later discovered that the transcriptional products of LIN-4 had antisense complementarity to multiple sites in the 30 untranslatable region (30 UTR) of LIN-14 messenger RNA (mRNA) [2,3]
The binding between these complementary regions decreased LIN-14 protein expression, which allowed for the progression of C. elegans development
Summary
MiRNAs, first discovered in 1993 by Lee and colleagues in the nematode Caenorhabditis elegans [1], are a category of ncRNAs that are 19–22nt in length and that function primarily by mediating post transcriptional gene silencing. First described as repeat-associated siRNAs, they were eventually named for their ability to form complexes with the P-element Induced Wimpy (PIWI) proteins of the Argonaute family, where they fit into specific binding pockets and serve as guides to lead the Argonaute protein to its target mRNA [7]. After their initial discovery in Drosophila, piRNA classes were found to be abundantly present in the gonads of various vertebrates and invertebrates [8], and were determined to play a key role in the suppression of transposon activity during germ line development [9]. While the various noncoding RNAs play unique roles in organisms’ development and function, their roles in cancer progression often overlap with individual members of the same RNA class, stimulating opposing pathways (Table 1)
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