Background
Chemoresistance is a major contributing factor to cancer treatment failure. Emerging research reveals that circular RNA (circRNA) dysregulation is implicated in chemoresistance. Our current study aimed to investigate the involvement of hsa_circ_0092887 in paclitaxel (PTX) resistance in non-small cell lung cancer (NSCLC).
Conclusion
Hsa_circ_0092887 depletion alleviated PTX-resistance in NSCLC cells via modulating the miR-490-5p/UBE2T axis, and the targeted management of hsa_circ_0092887-mediated signaling axis might contribute to PTX-resistance intervention in NSCLC.
Methods
RT-qPCR as well as western blotting were used for the analysis of hsa_circ_0092887, miR-490-5p and UBE2T expression in PTX-resistant NSCLC tumor tissues and cells. CCK-8 assay was done to determine the IC50 value of PTX. CCK-8 assay, wound healing assay, analysis of apoptosis related proteins (Bax and Bcl-2), and xenograft mouse models were utilized to investigate the role of hsa_circ_0092887 in PTX-resistance in NSCLC. The binding sites of miR-490-5p to hsa_circ_0092887 or UBE2T were predicted by bioinformatics tools and were verified by RIP and dual-luciferase assays.
Results
Expression of hsa_Circ_0092887 was upregulated in NSCLC tumor samples/cell lines, and its expression was also higher in PTX-resistant tumor samples/cell lines when compared with their respective controls. Silencing of hsa_circ_0092887 in PTX-treated NSCLC cells inhibited cell proliferation and migration, induced apoptosis, and suppressed tumor growth in xenograft mouse models in vivo. MiR-490-5p was a direct target of hsa_circ_0092887, and UBE2T was a functional downstream target of hsa_circ_0092887/miR-490-5p axis. Hsa_circ_0092887 depletion-induced anti-cancer effects in PTX-treated NSCLC cells were reversed by miR-490-5p inhibitor. Furthermore, inhibition of miR-490-5p strengthened UBE2T expression, thereby attenuating the anti-cancer effects caused by UBE2T knockdown.