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Induction of cancer-related microRNA expression profiling using excretory-secretory products of Clonorchis sinensis
- Source :
- Parasitology research. 113(12)
- Publication Year :
- 2014
-
Abstract
- Clonorchis sinensis is a carcinogenic human liver fluke by which chronic infection is strongly associated with the development of cholangiocarcinoma. Although this cholangiocarcinoma is caused by both physical and chemical irritation from direct contact with adult worms and their excretory–secretory products (ESPs), the precise molecular events of the host–pathogen interactions remain to be elucidated. To better understand the effect of C. sinensis infection on cholangiocarcinogenesis, we profiled the kinetics of changes in cancer-related microRNAs (miRNAs) in human cholangiocarcinoma cells (HuCCT1) treated with C. sinensis ESPs for different periods. Using miRNA microarray chips containing 135 cancer-related miRNAs, we identified 16 miRNAs showing differentially altered expression following ESP exposure. Of these miRNAs, 13 were upregulated and 3 were downregulated in a time-dependent manner compared with untreated controls. Functional clustering of these dysregulated miRNAs revealed involvement in cell proliferation, inflammation, oncogene activation/suppression, migration/invasion/metastasis, and DNA methylation. In particular, decreased expression of let-7i, a tumor suppressor miRNA, was found to be associated with the ESP-induced upregulation of TLR4 mRNA and protein, which contribute to host immune responses against liver fluke infection. Further real-time quantitative PCR analysis using ESP-treated normal cholangiocytes (H69) revealed that the expressions of nine miRNAs (miR-16-2, miR-93, miR-95, miR-153, miR-195, miR-199-3P, let7a, let7i, and miR-124a) were similarly regulated, indicating that the cell proliferation and inhibition of tumor suppression mediated by these miRNAs is common to both cancerous and non-cancerous cells. These findings constitute further our understanding of the multiple cholangiocarcinogenic pathways triggered by liver fluke infection.
- Subjects :
- Transcriptional Activation
Down-Regulation
Real-Time Polymerase Chain Reaction
Cholangiocarcinoma
Downregulation and upregulation
Cell Line, Tumor
microRNA
Animals
Humans
RNA, Messenger
Cell Proliferation
Regulation of gene expression
Clonorchis sinensis
General Veterinary
biology
Microarray analysis techniques
General Medicine
Helminth Proteins
biology.organism_classification
Microarray Analysis
Up-Regulation
Gene expression profiling
Gene Expression Regulation, Neoplastic
MicroRNAs
Infectious Diseases
Real-time polymerase chain reaction
Bile Ducts, Intrahepatic
Bile Duct Neoplasms
Insect Science
DNA methylation
Immunology
Host-Pathogen Interactions
Cancer research
Clonorchiasis
Parasitology
Subjects
Details
- ISSN :
- 14321955
- Volume :
- 113
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Parasitology research
- Accession number :
- edsair.doi.dedup.....1f911850e3869ba6b0a7c87f5b4982c3