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Screening and molecular mechanism research on bile microRNAs associated with chemotherapy efficacy in perihilar cholangiocarcinoma

ABSTRACT: Screening and molecular mechanism research on bile microRNAs associated with chemotherapy efficacy in perihilar cholangiocarcinoma

PROVIDER: PRJNA1180550 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR31182571_1.fastq.gz	Fastqsanger.gz
	SRR31182571_2.fastq.gz	Fastqsanger.gz
	SRR31182572_1.fastq.gz	Fastqsanger.gz
	SRR31182572_2.fastq.gz	Fastqsanger.gz
	SRR31182573_1.fastq.gz	Fastqsanger.gz

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Screening and molecular mechanism research on bile microRNAs associated with chemotherapy efficacy in perihilar cholangiocarcinoma

Project description:The efficacy of hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin (OXA) and 5-fluorouracil (5-Fu) for treating advanced perihilar cholangiocarcinoma (pCCA) has been demonstrated, yet the survival benefits of HAIC for pCCA patients vary. Here, we aimed to screen out HAIC resistance-related bile microRNAs (miRNAs) and explore the functions of specific bile miRNAs in pCCA based on high-throughput sequencing. Levels of bile miR-532-3p,miR-1250-5p, and miR-4772-5p were related to the survival of advanced pCCA patients after HAIC. However, only overexpression of miR-532-3p promoted OXA/5-Fu resistance, and downregulation of its expression improved sensitivity to OXA/5-Fu. Mechanistic investigations revealed secreted protein acidic and rich in cysteine (SPARC) as the direct target of miR-532-3p. Our study reveals that bile miR-532-3p, miR-1250-5p, and miR-4772-5p may serve as survival biomarkers in advanced pCCA patients after HAIC and that bile miR-532-3p promotes resistance to HAIC with OXA and 5-Fu via negatively regulating SPARC expression.

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Project description:To identify miRNAs differentially expressed in cholangiocarcinoma,3 human cholangiocarcinoma and their corresponding normal bile duct tissues were obtained from 3 patients after operation with postoperative pathological diagnosed perihilar or distal biliary cholangiocarcinoma miRNAs expression in human cholangiocarcinoma/normal bile duct samples was measured after operation.Three independent experiments were performed using different patients for each experiment.

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Project description:CCLP cholangiocarcinoma cells were transfected with CTRL inhibitor or MIR1249 inhibitor for 48 hours and treated with DMSO or chemotherapy (cisplatin and gemcitabine) for 48 hours before being collected and analysed for gene expression

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Project description:Cholangiocarcinoma (CCA) is a type of highly aggressive cancer arising from the biliary system. Through serum exosome miRNA sequencing, we screened out the differentially expressed miRNA in patients with cholangiocarcinoma(CCA) and common bile duct stones(CBDS).

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Project description:Cholangiocarcinoma is a cancer of the hepatic bile ducts that is typically detected at a stage too advanced for resection. Additionally, chemotherapy is of limited efficacy, hence, novel therapeutic approaches are urgently required, including targeting of the cancer stroma. A macrophage-derived signal, tumour necrosis factor-like weak inducer of apoptosis (TWEAK), binds to cell-surface fibroblast growth factor-inducible 14 (Fn14), on cholangiocarcinoma cells to induce cytokine and chemokine expression and secretion. These TWEAK-inducible factors from cholangiocarcinoma cells can also affect macrophage polarisation. We characterised proteins secreted by four well-characterised human cholangiocarcinoma cell lines in the presence or absence of recombinant human TWEAK (100 ng/ml), to discover novel TWEAK-inducible factors that could drive pro-tumour niche formation.

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