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• W4386315211 abstract "Abstract Background and aim: Intrahepatic cholangiocarcinoma (ICC) is a highly malignant subtype of cholangiocarcinoma (CCA) with a poor prognosis and limited therapeutic effectiveness, prompting further study to develop novel therapies for ICC. Tumor growth and tumor chemoresistance have been reported to be associated with ferroptosis. Circular RNAs (circRNAs) are involved in the regulation of ferroptosis and tumor progression. Here we report a novel circCRIM1 and uncover the mechanistic involved in ICC pathogenesis. Methods In 3 pairs of ICC tissues and adjacent normal tissues, RNAseq was conducted to identify differentially expressed circRNAs. Further validation of circCRIM1 (hsa_circ_0007386) expression in ICC tissues and cell lines was performed with qRT-PCR, and we examined the effects of knockdown or overexpression of circCRIM1 on tumor growth, chemoresistance, and signaling pathway activity in human CCA cell lines in vitro. The mechanism of circCRIM1 regulatory role was predicted by silico analysis, and validated by luciferase reporter assays, RIP assays, RNA pull-down assays, and FISH. Ferroptosis levels in ICC cells were detected by BODIPY 581/591 C11, Lipid ROS, FerroOrange and malondialdehyde (MDA) assays, and the relationship between circCRIM1 and ferroptosis was evaluated. Results CircCRIM1 was verified to be significantly higher in ICC tissues and cell lines, and its expression is negatively relative to survival and recurrence of ICC patients. Knockdown of circCRIM1 inhibited ICC progression, while overexpression of circCRIM1 showed the opposite trends. Mechanistically, by sponging miR-124-5p, circCRIM1 up-regulates the expression of thioredoxin reductase 1 (TXNRD1) which inhibiting ferroptosis, and ultimately affect the progression of ICC. Conclusion CircCRIM1 can be used as a therapeutic target in the treatment of ICC." @default.
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• W4386315211 date "2023-08-31" @default.
• W4386315211 modified "2023-10-13" @default.
• W4386315211 title "CircCRIM1 promotes intrahepatic cholangiocarcinoma progression by inhibiting ferroptosis via miR-124-5p/TXNRD1 axis" @default.
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• W4386315211 doi "https://doi.org/10.21203/rs.3.rs-3301674/v1" @default.
• W4386315211 hasPublicationYear "2023" @default.
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