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Oncogenic changes and EMT in normal human bile duct epithelial cells are caused by parasite-derived materials and N-nitrosodimethylamine

ABSTRACT: A total of 1,301 differentially expressed genes were identified: 521 upregulated and 780 downregulated. Furthermore, p21 and PAI levels decreased, which coincided with decreases in E-cadherin and increases in fibronectin expression, in cells stimulated with Clonorchis sinensis excretory/secretory products (ESPs) and NDMA. Cancer-related proteins, such as EGFR, K-ras, and PCNA, were significantly upregulated in cells exposed to C. sinensis ESPs and NDMA. Our results showed that C. sinensis ESPs and a small amount of NDMA were sufficient to induce cancerous transformation and epithelial-mesenchymal transition (EMT) in normal H69 cholangiocytes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE138806 | GEO | 2019/10/14

REPOSITORIES: GEO

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Project description:Clonorchis sinensis is a zoonotic parasite causing clonorchiasis associated with human diseases such as biliary calculi, cholecystitis, liver cirrhosis, and is classified as carcinogenic to humans for cholangiocarcinoma. MicroRNAs (miRNAs) are non-coding, regulating small RNA molecules essential for the complex life cycle of parasites and involved in parasitic infections. To identify and characterize miRNAs expressed in adult C. sinensis residing chronically in the biliary tract, we developed an integrative approach combining deep sequencing, bioinformatic predictions with stem-loop real-time PCR analysis. Here we report the use of this approach to identify and clone 6 new and 62,512 conserved C. sinensis miRNAs which belong to 284 families. There is strong bias on families, family members and sequence nucleotides in C. sinensis. Uracil is the dominant nucleotide, particularly at positions 1, 14 and 22, which were located approximately at the beginning, middle and the end of conserved miRNAs. There is no significant M-bM-^@M-^\seed regionM-bM-^@M-^] at the first and ninth positions commonly found in human, animals and plants. Categorization of conserved miRNAs indicated that miRNAs of C. sinensis are still innovated and concentrated along three branches of the phylogenetic tree leading to bilaterians, insects and coelomates. There are two miRNA strategies in C. sinensis for its parasitic life: keeping a large category of miRNA families of different animals and keeping a stringent conserved seed region with high active innovation in other place of miRNA mainly in the middle and the end, which are perfect for the parasite to perform its complex life style and for host changes. The present study represents the first large scale characterization of C. sinensis miRNAs, which have implications for understanding the complex biology of this zoonotic parasite, as well as the miRNA studies of other related species such as Opisthorchis felineus and O. viverrini of human and animal health significance. Analysis of miRNA profile in parasite of C. sinensis

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Oncogenic changes and EMT in normal human bile duct epithelial cells are caused by parasite-derived materials and N-nitrosodimethylamine

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