Publication: Dysregulated microRNA expression profiles in cholangiocarcinoma cell-derived exosomes
Issued Date
2018-10-01
Resource Type
ISSN
18790631
00243205
00243205
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2-s2.0-85052535664
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Mahidol University
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SCOPUS
Bibliographic Citation
Life Sciences. Vol.210, (2018), 65-75
Suggested Citation
Sarunya Kitdumrongthum, Chanatip Metheetrairut, Varodom Charoensawan, Puey Ounjai, Keatdamrong Janpipatkul, Wittaya Panvongsa, Jittima Weerachayaphorn, Pawinee Piyachaturawat, Arthit Chairoungdua Dysregulated microRNA expression profiles in cholangiocarcinoma cell-derived exosomes. Life Sciences. Vol.210, (2018), 65-75. doi:10.1016/j.lfs.2018.08.058 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/45038
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Title
Dysregulated microRNA expression profiles in cholangiocarcinoma cell-derived exosomes
Abstract
© 2018 Elsevier Inc. Aim: Cholangiocarcinoma (CCA) is a malignant tumor of bile duct epithelial cells. The prognosis of CCA is poor due to lack of effective therapeutic targets and detection at an advanced stage. Exosomes are secreted nano-sized vesicles and contribute to the malignancy of several cancers via transferring their miRNAs between cells. Thus, exosomal miRNAs may serve as new therapeutic targets and potential biomarkers for CCA. Main methods: Exosomes were isolated from three different CCA cell lines and normal human cholangiocyte cells, followed by miRNA profiling analysis. Potential role of dysregulated miRNA was investigated by knockdown experiment. Key findings: We found that 38 and 460 miRNAs in CCA exosomes were significantly up- and down-regulated, respectively. Of these differentially expressed miRNAs, the hsa-miR-205-5p and miR-200 family members were markedly up-regulated for 600–1500 folds, whereas the miR-199 family members and their clustered miRNA, hsa-miR-214-3p, were down-regulated for 1000–2000 folds. The expression patterns of these representative exosomal miRNAs were similar to those observed in all types of CCA cells. The target genes of the top ten most up- and down-regulated miRNAs are significantly associated with well-characterized cancer-related pathways. Consistently, knockdown of the most up-regulated miRNA, miR-205-5p, reduced KKU-M213 cell invasion and migration. Significance: We have demonstrated the distinct miRNA signatures in exosomes released from CCA cells, compared to normal human cholangiocyte cells. These exosomal miRNAs may have the potential to be novel therapeutic targets and biomarkers for CCA.