LAUSR

Osimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for lung adenocarcinoma (LUAD) harboring activating mutations, but patients ultimately develop acquired resistance. Circular RNAs are involved in EGFR-TKI resistance, while the role of hsa_circ_0005576 in the osimertinib resistance of LUAD remain unknown. In this study, we demonstrated that hsa_circ_0005576 could facilitate the osimertinib-resistant LUAD cells. Briefly, knockdown of hsa_circ_0005576 not only suppressed the proliferation and promoted the apoptosis of resistant LUAD cells, but also increased its sensitivity to osimertinib. Mechanistically, hsa_circ_0005576, serving as a miRNA-sponge, could directly interact with miR-512-5p and subsequently upregulate the miR-512-5p-targeted insulin-like growth factor 1 receptor (IGF1R). The rescue assays indicated that miR-512-5p inhibition could reverse the effects of hsa_circ_0005576 knockdown on LUAD cells resistance to osimertinib. Overall, our study revealed that hsa_circ_0005576 regulates proliferation and apoptosis through miR-512-5p/IGF1R signaling, further which contributes to resistance of LUAD cells to osimertinib. Meanwhile, it provides a novel insight on the mechanism underlying osimertinib resistance of LUAD.