MicroRNA-144 suppresses cholangiocarcinoma cell proliferation and invasion through targeting platelet activating factor acetylhydrolase isoform 1b

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.

MiR‐144‐3p regulates osteogenic differentiation and proliferation of murine mesenchymal stem cells by specifically targeting Smad4

“…2). As several previous studies reported, miR-144-3p suppressed the cell proliferation of different tumour cells by inhibiting cancer-relevant genes [31,32], which was consistent with the present study in that miR-144-3p inhibited the proliferation of cells by arresting the C3H10T1/2 cells in the G0/G1 phase (Fig. 3).…”

Molecular Mechanisms Driving Cholangiocarcinoma Invasiveness: An Overview

“…miRNAs affect a variety of cell processes related to tumor biology, including cell motility. Specifically, miR-34a 163 , miR-122 164 , miR-140-5p 165 , miR-144 162 , miR-200c 166 , miR-204 167 , miR-212 168 , miR-214 169 , and miR-605 170 negatively regulate CCA cell migration/invasion and consistently, are frequently down-regulated in neoplastic bile ducts. Conversely, miR-21 161,171,172 , miR-181c 173 , and miR-221 174 are up-regulated in CCA, and promote the gain of invasive functions by cancer cells.…”

“…In this regard, several miRNAs were found to be deregulated in CCA cell lines 159 and tissues 160–162 , with the majority of them being under-expressed. miRNAs affect a variety of cell processes related to tumor biology, including cell motility.…”

Deregulated MicroRNAs in Biliary Tract Cancer: Functional Targets and Potential Biomarkers

“…Interestingly, another study described LIS1 as a driver of cell migration and invasive potential of lung cancer cells [67]. In line with this study, Yang et al demonstrated that LIS1 is a direct target of miRNA-144 in BTC and, furthermore, they showed that ectopic expression of miRNA-144 diminished LIS1 expression [66]. Combined with their observation that knockdown of LIS1 reduced invasion of CC cells, miRNA-144 is yet another miRNA whose downregulation in CC can result in enhanced metastatic potential.…”

“…MBD2 is involved in the DNA methylation-dependent repression of gene transcription as a reader of cytosine methylation and was suggested as a marker associated with poor prognosis for patients with hepatocellular carcinoma [64, 65]. MicroRNA-144 is another miRNA species found to be downregulated in CC tissues compared to nonmalignant tissues as well as in CC cell lines versus nonmalignant cells [66]. Although no clinicopathological features that are associated with deregulated miRNA-144 expression were presented in this study, the authors clearly demonstrate an inverse expression pattern of miRNA-144 (low expression) and LIS1 (high expression) in CC patient samples.…”