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Circular RNA circ_0000376 promotes paclitaxel resistance and tumorigenesis of non‐small cell lung cancer via positively modulating KPNA4 by sponging miR‐1298‐5p
BACKGROUND: Circ_0000376 could promote non‐small cell lung cancer (NSCLC) progression; however, the role of circ_0000376 in paclitaxel (PTX) resistance of NSCLC is still unknown. METHODS: Quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blot were applied for measuring circ_0000...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons Australia, Ltd
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10396781/ https://www.ncbi.nlm.nih.gov/pubmed/37455373 http://dx.doi.org/10.1111/1759-7714.14994 |
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author | Hu, Sheng Zhang, Qun Sun, Jian Xue, Jinshan Wang, Can |
author_facet | Hu, Sheng Zhang, Qun Sun, Jian Xue, Jinshan Wang, Can |
author_sort | Hu, Sheng |
collection | PubMed |
description | BACKGROUND: Circ_0000376 could promote non‐small cell lung cancer (NSCLC) progression; however, the role of circ_0000376 in paclitaxel (PTX) resistance of NSCLC is still unknown. METHODS: Quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blot were applied for measuring circ_0000376, microRNA‐1298‐5p (miR‐1298‐5p), and karyopherin subunit alpha 4 (KPNA4) expression. The half inhibitory concentration (IC50) of PTX was assessed by cell counting kit‐8 assay. 5‐ethynyl‐2′‐deoxyuridine assay, wound healing assay, transwell assay, and flow cytometry were performed to measure the proliferation, migration, invasion, and apoptosis of cells. The regulatory mechanisms of circ_0000376, miR‐1298‐5p, and KPNA4 were validated by dual‐luciferase reporter assay, RNA immunoprecipitation assay, and rescue experiments. Xenograft assay was used for the functional analysis of circ_0000376 in vivo. RESULTS: Circ_0000376 and KPNA4 expressions were upregulated, while miR‐1298‐5p expression was downregulated in PTX‐resistant tissues and cells. Circ_0000376 depletion promoted PTX sensitivity and apoptosis, while suppressing the proliferation, migration, and invasion of PTX‐resistant NSCLC cells. Furthermore, circ_0000376 could modulate KPNA4 expression by sponging miR‐1298‐5p. Rescue experiments showed that miR‐1298‐5p inhibition reversed the circ_0000376 depletion‐mediated anticancer effects and PTX sensitivity. Moreover, miR‐1298‐5p inhibited PTX resistance and tumorigenesis of PTX‐resistant cells, which were abolished by KPNA4 overexpression. In addition, circ_0000376 knockdown suppressed tumor growth and enhanced PTX sensitivity in vivo. CONCLUSION: Circ_0000376 facilitated PTX resistance and tumorigenesis of NSCLC by miR‐1298‐5p/KPNA4 axis, suggesting an underlying therapeutic strategy for NSCLC. |
format | Online Article Text |
id | pubmed-10396781 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley & Sons Australia, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-103967812023-08-04 Circular RNA circ_0000376 promotes paclitaxel resistance and tumorigenesis of non‐small cell lung cancer via positively modulating KPNA4 by sponging miR‐1298‐5p Hu, Sheng Zhang, Qun Sun, Jian Xue, Jinshan Wang, Can Thorac Cancer Original Articles BACKGROUND: Circ_0000376 could promote non‐small cell lung cancer (NSCLC) progression; however, the role of circ_0000376 in paclitaxel (PTX) resistance of NSCLC is still unknown. METHODS: Quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blot were applied for measuring circ_0000376, microRNA‐1298‐5p (miR‐1298‐5p), and karyopherin subunit alpha 4 (KPNA4) expression. The half inhibitory concentration (IC50) of PTX was assessed by cell counting kit‐8 assay. 5‐ethynyl‐2′‐deoxyuridine assay, wound healing assay, transwell assay, and flow cytometry were performed to measure the proliferation, migration, invasion, and apoptosis of cells. The regulatory mechanisms of circ_0000376, miR‐1298‐5p, and KPNA4 were validated by dual‐luciferase reporter assay, RNA immunoprecipitation assay, and rescue experiments. Xenograft assay was used for the functional analysis of circ_0000376 in vivo. RESULTS: Circ_0000376 and KPNA4 expressions were upregulated, while miR‐1298‐5p expression was downregulated in PTX‐resistant tissues and cells. Circ_0000376 depletion promoted PTX sensitivity and apoptosis, while suppressing the proliferation, migration, and invasion of PTX‐resistant NSCLC cells. Furthermore, circ_0000376 could modulate KPNA4 expression by sponging miR‐1298‐5p. Rescue experiments showed that miR‐1298‐5p inhibition reversed the circ_0000376 depletion‐mediated anticancer effects and PTX sensitivity. Moreover, miR‐1298‐5p inhibited PTX resistance and tumorigenesis of PTX‐resistant cells, which were abolished by KPNA4 overexpression. In addition, circ_0000376 knockdown suppressed tumor growth and enhanced PTX sensitivity in vivo. CONCLUSION: Circ_0000376 facilitated PTX resistance and tumorigenesis of NSCLC by miR‐1298‐5p/KPNA4 axis, suggesting an underlying therapeutic strategy for NSCLC. John Wiley & Sons Australia, Ltd 2023-07-16 /pmc/articles/PMC10396781/ /pubmed/37455373 http://dx.doi.org/10.1111/1759-7714.14994 Text en © 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Hu, Sheng Zhang, Qun Sun, Jian Xue, Jinshan Wang, Can Circular RNA circ_0000376 promotes paclitaxel resistance and tumorigenesis of non‐small cell lung cancer via positively modulating KPNA4 by sponging miR‐1298‐5p |
title | Circular RNA circ_0000376 promotes paclitaxel resistance and tumorigenesis of non‐small cell lung cancer via positively modulating KPNA4 by sponging miR‐1298‐5p |
title_full | Circular RNA circ_0000376 promotes paclitaxel resistance and tumorigenesis of non‐small cell lung cancer via positively modulating KPNA4 by sponging miR‐1298‐5p |
title_fullStr | Circular RNA circ_0000376 promotes paclitaxel resistance and tumorigenesis of non‐small cell lung cancer via positively modulating KPNA4 by sponging miR‐1298‐5p |
title_full_unstemmed | Circular RNA circ_0000376 promotes paclitaxel resistance and tumorigenesis of non‐small cell lung cancer via positively modulating KPNA4 by sponging miR‐1298‐5p |
title_short | Circular RNA circ_0000376 promotes paclitaxel resistance and tumorigenesis of non‐small cell lung cancer via positively modulating KPNA4 by sponging miR‐1298‐5p |
title_sort | circular rna circ_0000376 promotes paclitaxel resistance and tumorigenesis of non‐small cell lung cancer via positively modulating kpna4 by sponging mir‐1298‐5p |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10396781/ https://www.ncbi.nlm.nih.gov/pubmed/37455373 http://dx.doi.org/10.1111/1759-7714.14994 |
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