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Circ_0031242 Silencing Mitigates the Progression and Drug Resistance in DDP-Resistant Hepatoma Cells by the miR-924/POU3F2 Axis
BACKGROUND: Circular RNAs (circRNAs) have been implicated in the progression and chemoresistance development of hepatocellular carcinoma (HCC). However, the precise parts of circ_0031242 in HCC chemoresistance are still not fully understood. METHODS: The levels of circ_0031242, miR-924 and POU class...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847388/ https://www.ncbi.nlm.nih.gov/pubmed/33531841 http://dx.doi.org/10.2147/CMAR.S272851 |
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author | Fan, Wei Chen, Lei Wu, Xiaojuan Zhang, Tong |
author_facet | Fan, Wei Chen, Lei Wu, Xiaojuan Zhang, Tong |
author_sort | Fan, Wei |
collection | PubMed |
description | BACKGROUND: Circular RNAs (circRNAs) have been implicated in the progression and chemoresistance development of hepatocellular carcinoma (HCC). However, the precise parts of circ_0031242 in HCC chemoresistance are still not fully understood. METHODS: The levels of circ_0031242, miR-924 and POU class 3 homeobox 2 (POU3F2) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) assay or Western blot analysis. IC(50) value for cisplatin (DDP) and cell viability were measured by the cell counting kit-8 (CCK-8) assay. Cell migration, invasion and apoptosis were assessed by transwell assay and flow cytometry, respectively. Targeted correlations among circ_0031242, miR-924 and POU3F2 were verified by the dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. RESULTS: Our data revealed that circ_0031242 was associated with HCC resistance to DDP. The silencing of circ_0031242 diminished DDP resistance, suppressed cell viability, migration, invasion and promoted apoptosis of DDP-resistant HCC cells (Huh7-R and SNU-387-R) in vitro, as well as enhanced DDP sensitivity in vivo. Mechanistically, circ_0031242 directly interacted with miR-924 by binding to miR-924. Moreover, miR-924 was a downstream effector of circ_0031242 function. POU3F2 was a direct target of miR-924, and miR-924 overexpression regulated DDP-resistant HCC cell progression and DDP resistance by down-regulating POU3F2. Furthermore, circ_0031242 modulated POU3F2 expression through sponging miR-924. CONCLUSION: Our findings identified that circ_0031242 functioned as an important regulator in DDP-resistant HCC cell progression and DDP resistance through the miR-924/POU3F2 axis, illuminating circ_0031242 as a potential therapeutic target for the chemoresistant HCC. |
format | Online Article Text |
id | pubmed-7847388 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-78473882021-02-01 Circ_0031242 Silencing Mitigates the Progression and Drug Resistance in DDP-Resistant Hepatoma Cells by the miR-924/POU3F2 Axis Fan, Wei Chen, Lei Wu, Xiaojuan Zhang, Tong Cancer Manag Res Original Research BACKGROUND: Circular RNAs (circRNAs) have been implicated in the progression and chemoresistance development of hepatocellular carcinoma (HCC). However, the precise parts of circ_0031242 in HCC chemoresistance are still not fully understood. METHODS: The levels of circ_0031242, miR-924 and POU class 3 homeobox 2 (POU3F2) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) assay or Western blot analysis. IC(50) value for cisplatin (DDP) and cell viability were measured by the cell counting kit-8 (CCK-8) assay. Cell migration, invasion and apoptosis were assessed by transwell assay and flow cytometry, respectively. Targeted correlations among circ_0031242, miR-924 and POU3F2 were verified by the dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. RESULTS: Our data revealed that circ_0031242 was associated with HCC resistance to DDP. The silencing of circ_0031242 diminished DDP resistance, suppressed cell viability, migration, invasion and promoted apoptosis of DDP-resistant HCC cells (Huh7-R and SNU-387-R) in vitro, as well as enhanced DDP sensitivity in vivo. Mechanistically, circ_0031242 directly interacted with miR-924 by binding to miR-924. Moreover, miR-924 was a downstream effector of circ_0031242 function. POU3F2 was a direct target of miR-924, and miR-924 overexpression regulated DDP-resistant HCC cell progression and DDP resistance by down-regulating POU3F2. Furthermore, circ_0031242 modulated POU3F2 expression through sponging miR-924. CONCLUSION: Our findings identified that circ_0031242 functioned as an important regulator in DDP-resistant HCC cell progression and DDP resistance through the miR-924/POU3F2 axis, illuminating circ_0031242 as a potential therapeutic target for the chemoresistant HCC. Dove 2021-01-26 /pmc/articles/PMC7847388/ /pubmed/33531841 http://dx.doi.org/10.2147/CMAR.S272851 Text en © 2021 Fan et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Fan, Wei Chen, Lei Wu, Xiaojuan Zhang, Tong Circ_0031242 Silencing Mitigates the Progression and Drug Resistance in DDP-Resistant Hepatoma Cells by the miR-924/POU3F2 Axis |
title | Circ_0031242 Silencing Mitigates the Progression and Drug Resistance in DDP-Resistant Hepatoma Cells by the miR-924/POU3F2 Axis |
title_full | Circ_0031242 Silencing Mitigates the Progression and Drug Resistance in DDP-Resistant Hepatoma Cells by the miR-924/POU3F2 Axis |
title_fullStr | Circ_0031242 Silencing Mitigates the Progression and Drug Resistance in DDP-Resistant Hepatoma Cells by the miR-924/POU3F2 Axis |
title_full_unstemmed | Circ_0031242 Silencing Mitigates the Progression and Drug Resistance in DDP-Resistant Hepatoma Cells by the miR-924/POU3F2 Axis |
title_short | Circ_0031242 Silencing Mitigates the Progression and Drug Resistance in DDP-Resistant Hepatoma Cells by the miR-924/POU3F2 Axis |
title_sort | circ_0031242 silencing mitigates the progression and drug resistance in ddp-resistant hepatoma cells by the mir-924/pou3f2 axis |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847388/ https://www.ncbi.nlm.nih.gov/pubmed/33531841 http://dx.doi.org/10.2147/CMAR.S272851 |
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