Wei Zhang1, Chao Song2, Xiaona Ren2. 1. Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan City, Shandong Province, China. 2. Department of Pharmacy, Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Jinan City, Shandong Province, China.
Abstract
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.
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.