Abstract
Numerous work has revealed the involvement of circular RNA (circRNA) in regulating chemotherapy resistance. Here, we investigate circPIM3 role in taxol (Tax) resistance in non-small cell lung cancer (NSCLC). CircPIM3, microRNA (miR)-338-3p and tumor necrosis factor-alpha-induced protein-8 (TNFAIP8) expression were detected via quantitative real-time PCR, western blot or immunohistochemistry assay. Tax resistance was evaluated using cell counting kit-8, cell proliferation was measured by colony formation assay, cell cycle and apoptosis were examined via flow cytometry. The interplay between miR-338-3p and circPIM3 or TNFAIP8 was confirmed by dual-luciferase reporter assay. Finally, the effect of circPIM3 on Tax resistance in NSCLC in vivo was investigated by xenograft models. CircPIM3 and TNFAIP8 were upregulated in Tax-resistant NSCLC tissue and cell samples. Reducing circPIM3 expression inhibited Tax resistance, proliferation and induced cycle arrest and apoptosis in Tax-resistant NSCLC cells. Mechanically, circPIM3 absence led to downregulation of TNFAIP8 via absorbing miR-338-3p. Additionally, circPIM3 depletion increased Tax sensitivity of NSCLC in vivo. Silencing of circPIM3 suppressed Tax resistance in Tax-resistant NSCLC cells through regulation of the miR-338-3p/TNFAIP8 axis.
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