Circ_0003998 Regulates the Progression and Docetaxel Sensitivity of DTX-Resistant Non-Small Cell Lung Cancer Cells by the miR-136-5p/CORO1C Axis

BACKGROUND: Drug resistance in cancer cells is a major challenge for anti-cancer therapy. Circular RNA (circRNA) circ_0003998 has been identified as an important regulator in the chemoresistance development of non-small cell lung cancer (NSCLC). The purpose of this study was to investigate the molecular basis underlying the resistance control of circ_0003998 in NSCLC. METHODS: The levels of circ_0003998, miR-136-5p and coronin 1C (CORO1C) were gauged by the quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Cell viability, colony formation and apoptosis were evaluated by the Cell Counting Kit-8 (CCK-8), colony formation and flow cytometry assays, respectively. Targeted relationships among circ_0003998, miR-136-5p and CORO1C were confirmed by the dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Animal studies were performed to evaluate the function of circ_0003998 in vivo. RESULTS: Our data indicated that circ_0003998 expression was associated with NSCLC resistance to docetaxel (DTX). The knockdown of circ_0003998 promoted DTX sensitivity, suppressed cell colony formation, and enhanced cell apoptosis of A549/DTX and H1299/DTX cells in vitro. Moreover, circ_0003998 knockdown hampered tumor growth and enhanced DTX sensitivity in vivo. Mechanistically, circ_0003998 directly targeted miR-136-5p, and miR-136-5p was a molecular mediator of circ_0003998 function in vitro. Furthermore, CORO1C was a functionally important target of miR-136-5p in regulating DTX-resistant NSCLC cell colony formation, apoptosis and DTX sensitivity in vitro. Additionally, circ_0003998 modulated CORO1C expression by working as a miR-136-5p sponge. CONCLUSION: Our present work identified that circ_0003998 regulated DTX-resistant NSCLC cell colony formation, apoptosis and DTX sensitivity at least partially by controlling CORO1C expression by sponging miR-136-5p, illuminating a rationale for developing circ_0003998 as a therapeutic target of chemoresistant NSCLC.