Abstract
BackgroundMicroRNAs are endogenous non-coding RNAs that play important roles in a wide variety of biological processes such as apoptosis, development, aging and cancer. The aberrant expression of miRNAs may contribute to phenotypic features of malignant cells, including resistance to chemotherapy. However, in cholangiocarcinoma (CCA) the correlation between miRNAs and their potential roles in CCA remains unclear.MethodsMicroRNA profiles were analyzed in three pairs of CCA tumor specimens and non-tumorous-paired biliary tissues using Agilent microRNA microarrays. Expression of selected miRNAs was further confirmed in CCA tissues and CCA cell lines by q-PCR. The effects of miR-144 were evaluated by cell proliferation, migration, transwell, and tumorigenicity assays. Expression of LIS1 (platelet-activating factor acetylhydrolase isoform 1b) was assessed in CCA specimens and CCA cell lines by q-PCR and western blot. Targeting of LIS1 by miR-144 was confirmed by luciferase reporter assays.ResultsWe found that the expression of 28 miRNAs in CCA tissues was significantly different from their corresponding adjacent normal bile duct tissues. We focused on miR-144 which was significantly down-regulated in CCA tissues. Reintroduction of miR-144 in CCA cell lines not only inhibited cell growth, but also significantly reduced cell migration and invasion capacities compared with controls. Luciferase assays and western blots verified LIS1 as a direct target of miR-144, and knocking-down LIS1 has similar effect with overexpression of miR-144 in CCA cell lines. Moreover, overexpression of miR-144 expression could suppress tumor growth in nude mice.ConclusionsOur results showed that miR-144 was reduced in CCA tissues and suggested that miR-144 may be an essential suppresser of CCA cell proliferation and invasion through targeting LIS1.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-917) contains supplementary material, which is available to authorized users.
Highlights
MicroRNAs are endogenous non-coding RNAs that play important roles in a wide variety of biological processes such as apoptosis, development, aging and cancer
The miR-144-expressing vector (miR-144) is downregulated in CCA tissues and cell lines As miRNAs have critical functions in the regulation of many biological processes such as cell proliferation and metastasis, we compared the miRNA expression profiles between three pairs of CCA samples and the corresponding normal bile duct tissues
To study the possible role of miRNAs that inhibit CCA cell proliferation and metastasis, we focused on miR-144, as it is significantly downregulated in CCA samples
Summary
MicroRNAs are endogenous non-coding RNAs that play important roles in a wide variety of biological processes such as apoptosis, development, aging and cancer. Accumulating evidence indicates that aberrant expression of miRNAs contributes to a variety of biological processes including embryonic development and tumorigenesis [12,13,14,15]. Deregulated miRNAs have been identified that act as oncogenes or tumor suppressors [16,17,18,19,20,21,22]. These results suggest that miRNAs can contribute to tumor growth, the possible molecular mechanisms remain to be further elucidated
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