MicroRNAs in Hepatobiliary and Pancreatic Cancers

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that function as endogenous silencers of numerous target genes. Hundreds of miRNAs have been identified in the human genome. miRNAs are expressed in a tissue-specific manner and play important roles in cell proliferation, apoptosis, and differentiation. Aberrant expression of miRNAs may also contribute to the development and progression of human hepatobiliary and pancreatic cancers. Recent studies have shown that some miRNAs play roles as tumor suppressors or oncogenes in hepatobiliary and pancreatic cancers. miR-122, let-7 family, and miR-101 are down-regulated in hepatocellular carcinoma (HCC), suggesting that it is a potential tumor suppressor of HCC. miR-221 and miR-222 are up-regulated in HCC and may act as oncogenic miRNAs in hepatocarcinogenesis. miRNA expression profiling may be a powerful clinical tool for diagnosis and regulation of miRNA expression could be a novel therapeutic strategy for hepatobiliary and pancreatic cancers. In this review, we summarize current knowledge about the roles of important tumor suppressor microRNAs and oncogenic microRNAs in hepatobiliary and pancreatic cancers.

Mechanism of gemcitabine-induced suppression of human cholangiocellular carcinoma cell growth

“…Therefore, the antitumor effect of gemcitabine might be associated with miR-1260b inhibition. miR-222 was also recognized as oncogenic miRNA (39)(40)(41)(42)(43). The cell cycle-dependent kinase inhibitor, p27Kip1 is the target gene of miR-222 (39,40,43).…”

miR-122 regulates hepatic lipid metabolism and tumor suppression

“…The activity of miR-122 has previously been assessed through antisense oligonucleotide-mediated knockdown, implicating miR-122 in cholesterol and fat metabolism (4,5). Although HCC was not observed in the time frame of these studies, several groups have reported tumor suppressor activity for miR-122, based on decreased miR-122 levels in tumor tissue and inhibitory effects of miR-122 in tumorigenicity assays (6). However, knockdown experiments are limited by their transient nature and the potential for off-target effects.…”

“…Chemotherapeutic agents that inhibit neutrophil biogenesis (6)(7)(8) and/or reduce their bactericidal activity (7) produce neutropenia (i.e., <500,000 neutrophils/ml blood). Although neutropenia predisposes to infection, it has little direct effect on the sterility of blood because under most (9) -but not all (10) -conditions, hepatic and splenic macrophages are the cells primarily responsible for clearing bacteria from the circulation.…”

Regulation of the oncogenic function of distal-less 4 by microRNA-122 in hepatocellular carcinoma

“…This suggested that Bcl-w is a direct target of miR-122 that functions as an endogenous apoptosis enhancer in HCC cells (16). Other miR-122 target genes include SRF, Igf1R, ADAM10, ADAM17 in HCC (20). In the present study, a new miR-122/DLX4 axis was …”