Abstract
Circular RNAs (circRNAs) are key regulators in tumor metastasis and drug resistance. This study was designed to investigate circ_0082182 function and mechanism in oxaliplatin (OXA) resistance and cancer progression of colorectal cancer (CRC). The circ_0082182, microRNA-326 (miR-326), and nuclear factor I B (NFIB) levels were quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell sensitization was analyzed by Cell Counting Kit-8 assay. The proliferation ability was determined via EdU assay, and apoptosis was measured by flow cytometry. Transwell assay and wound healing assay were performed to assess cell invasion and migration. The protein level was examined through Western blot. The binding interaction was conducted via dual-luciferase reporter assay. Xenograft tumor assay was used to explore the circ_0082182 function in vivo. The circ_0082182 level was upregulated in OXA-resistant CRC samples and cells. Downregulation of circ_0082182 suppressed OXA resistance, proliferation, invasion, and migration but promoted apoptosis of OXA-resistant CRC cells. Circ_0082182 acted as a sponge for miR-326. The regulatory role of circ_0082182 was ascribed to the miR-326 sponging function. MiR-326 directly targeted NFIB to impede OXA resistance and cancer progression in CRC cells. NFIB level was regulated by circ_0082182 via sponging miR-326. Circ_0082182 promoted tumor growth in OXA-resistant xenograft tumor model through mediating the miR-326/NFIB axis. These data suggested that circ_0082182 elevated the NFIB expression to regulate OXA resistance and CRC progression by absorbing miR-326.
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All the authors have been involved in the management of the patient and in the conception of the manuscript. The specific authors’ contribution is as follows: WZF and LJM were involved in writing the drafting of the manuscript; YT collected data; WQQ performed analysis and interpretation; LR provided software; and TJL contributed to reviewing and editing.
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Wang, Z., Liu, J., Yang, T. et al. Circ_0082182 upregulates the NFIB level via sponging miR-326 to promote oxaliplatin resistance and malignant progression of colorectal cancer cells. Mol Cell Biochem 478, 1045–1057 (2023). https://doi.org/10.1007/s11010-022-04551-9
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DOI: https://doi.org/10.1007/s11010-022-04551-9