Open AccessBlocking circ_0014130 suppressed drug resistance and malignant behaviors of docetaxel resistance-acquired NSCLC cells via regulating miR-545-3p-YAP1 axis
Author(s) -
Dongjie Du,
Xiaoci Cao,
Xinbo Duan,
Xianbo Zhang
Publication year - 2021
Publication title -
cytotechnology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.488
H-Index - 62
eISSN - 1573-0778
pISSN - 0920-9069
DOI - 10.1007/s10616-021-00478-z
Subject(s) - downregulation and upregulation , gene knockdown , docetaxel , cancer research , gene silencing , flow cytometry , competing endogenous rna , chemistry , apoptosis , microbiology and biotechnology , biology , cancer , medicine , long non coding rna , gene , biochemistry
Recent evidences have claimed that circular RNAs are deregulated in docetaxel (DTX) resistance in malignant tumors, including non-small-cell lung cancer (NSCLC). Hsa_circ_0014130 (circ_0014130) is a new biomarker in NSCLC. However, its role in DTX-resistant NSCLC remained to be annotated. In this study, real-time PCR was used to measure expression of circ_0014130, and circ_0014130 was upregulated in NSCLC tumors and DTX-resistant NSCLC cells (NCI-H1299/DTX and A549/DTX). MTT assay analyzed the half inhibitory concentration (IC50) of DTX, and it was lowered by circ_0014130 interference in DTX-resistant NSCLC cells. Moreover, colony formation assay, flow cytometry, transwell assays, and xenograft tumor model revealed that silencing circ_0014130 facilitated apoptosis rate of DTX-resistant NSCLC cells, suppressed the colony formation, migration and invasion, and retarded xenograft tumor growth in nude mice. Dual-luciferase reporter assay and RNA immunoprecipitation confirmed that circ_0014130 was one competing endogenous RNA (ceRNA) for miRNA (miR)-545-3p, and circ_0014130 modulated expression of yes-associated protein 1 (YAP1), a target gene for miR-545-3p. YAP1 upregulation and miR-545-3p downregulation were allied with circ_0014130 upregulation in NSCLC tumors and DTX-resistant NSCLC cells. Functionally, downregulating miR-545-3p could abate the effects of circ_0014130 knockdown in DTX-resistant NSCLC cells in vitro, whereas its overexpression exerted similar effects of circ_0014130 knockdown. Either, restoring YAP1 partially reversed miR-545-3p effects in DTX-resistant NSCLC cells. Collectively, there might be a novel circ_0014130-miR-545-3p-YAP1 ceRNA pathway in regulation of chemoresistance and malignant behaviors of DTX-resistant NSCLC cells, suggesting a potential therapeutic approach for DTX resistance.