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KMID : 1034820230190020383
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Molecular & Cellular Toxicology
2023 Volume.19 No. 2 p.383 ~ p.393
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Hsa_circ_0011292 regulates paclitaxel resistance partially through regulating CDCA4 expression by serving as a miR-3619-5p sponge in non-small cell lung cancer
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Yanan Bao
Yue Cui
Yumin Luan
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Abstract
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Background : Circular RNA hsa_circ_0011292 (circ_0011292) participates in NSCLC resistance to paclitaxel (PTX). Here, we further clarify the mechanism of circ_0011292 regulating non-small cell lung cancer (NSCLC) resistance to PTX.
Objectives : Expression patterns of circ_0011292, microRNA (miR)-3619-5p, and CDCA4 mRNA were verified by qRT-PCR. The IC50 (half-maximal inhibitory concentration) value, proliferation, migration, invasion, and apoptosis were analyzed by MTT, transwell, and flow cytometry assays. Protein levels were measured by western blotting (WB). The regulation mechanism of circ_0011292 was analyzed by bioinformatics analysis, dual-luciferase reporter, and/or RNA pull-down assays.
Results : Circ_0011292 was highly expressed in PTX-resistant NSCLC. Functionally, circ_0011292 inhibition lowered cell IC50 value, induced cell apoptosis, and repressed cell proliferation, migration, and invasion in PTX-resistant NSCLC cells in vitro. Mechanically, circ_0011292 acted as a decoy for miR-3619-5p, which targeted CDCA4 in PTX-resistant NSCLC cells. Both miR-3619-5p inhibitor and CDCA4 overexpression overturned circ_0011292 inhibition-mediated influence on PTX sensitivity and malignant behaviors of PTX-resistant NSCLC cells. Importantly, circ_0011292 adsorbed miR-3619-5p to regulate CDCA4 expression.
Conclusions : Circ_0011292 facilitates PTX resistance in NSCLC partially through the miR-3619-5p/CDCA4 pathway, highlighting a new mechanism responsible for PTX resistance in NSCLC.
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KEYWORD
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NSCLC, PTX, circ_0011292, miR-3619-5p, CDCA4
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