Circular RNA circ-CD44 regulates chemotherapy resistance by targeting the miR-330-5p/ABCC1 axis in colorectal cancer cells

• Shuai Zhao ^[1] ; Fei Xu ^[1] ; Yiding Ji ^[1] ; Yuanyuan Wang ^[1] ; Ming Wei ^[1] ; Like Zhang ^[1]
  1. [1] The First Hospital of Hebei Medical University, Shijiazhuang City, Hebei Province, China.
• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 38, Nº. 2, 2023, págs. 209-221
• Idioma: inglés
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• Resumen

  • Background. Colorectal cancer (CRC) is a common malignant tumor worldwide, ranking fourth for incidence. Recently, circular RNAs (circRNAs) have been demonstrated to play a key role in chemotherapy resistance to CRC treatment. Therefore, the role of circCD44 is investigated in CRC.

    Methods. The expression levels of circ-CD44, miR330-5p, and ATP binding cassette subfamily C member 1 (ABCC1) were quantified by real-time quantitative polymerase chain reaction (RT-qPCR) assay. The sensitivity of CRC cells to oxaliplatin (OXA) was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl2H-tetrazol-3-ium bromide (MTT) assay. Colonyforming experiment was performed to measure the colony-forming ability of CRC cells. The apoptosis, migration, and invasion of CRC cells were determined by flow cytometry and transwell assays. A xenograft experiment was established to clarify the functional role of circ-CD44 silencing in vivo. The interactional relationship among circ-CD44, miR-330-5p, and ABCC1 was confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. The protein expression of ABCC1 was quantified by western blot assay.

    Results. Circ-CD44 was obviously upregulated in OXA-resistant colorectal cancer tissues and cells. Lossof-function experiments revealed that inhibition of circCD44 suppressed proliferation, migration, and invasion while it increased OXA sensitivity and apoptosis in OXA-resistant colorectal cancer cells, which was overturned by suppression of miR-330-5p; besides, silencing of circ-CD44 also slowed the tumor growth in vivo. Additionally, overexpression of miR-330-5p inhibited chemotherapy resistance, proliferation, migration, and invasion while it induced apoptosis by targeting ABCC1.

    Conclusion. Mechanistically, circ-CD44 functioned as a miRNA sponge for miR-330-5p to upregulate the expression of ABCC1 and regulate chemotherapy resistance in CRC cells.