Circ_0003998 enhances doxorubicin resistance in hepatocellular carcinoma by regulating miR-218-5p/EIF5A2 pathway
Abstract Background The involvement of circular RNAs (circRNAs) in chemoresistance of tumors has been identified. Herein, this study aims to investigate the role and the underlying mechanism of circ_0003998 in doxorubicin (DOX) resistance in hepatocellular carcinoma (HCC). Methods The expression of...
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doaj-00ad70a284d04db394768d453b4e2dc92020-12-13T12:19:15ZengBMCDiagnostic Pathology1746-15962020-12-0115111310.1186/s13000-020-01056-1Circ_0003998 enhances doxorubicin resistance in hepatocellular carcinoma by regulating miR-218-5p/EIF5A2 pathwayXiaomin Li0Jiefeng He1Xiaojing Ren2Haichao Zhao3Haoliang Zhao4Shanxi Medical UniversityDepartment of General Surgery, Shanxi Bethune HospitalDepartment of General Surgery, Shanxi Bethune HospitalDepartment of General Surgery, Shanxi Bethune HospitalDepartment of General Surgery, Shanxi Bethune HospitalAbstract Background The involvement of circular RNAs (circRNAs) in chemoresistance of tumors has been identified. Herein, this study aims to investigate the role and the underlying mechanism of circ_0003998 in doxorubicin (DOX) resistance in hepatocellular carcinoma (HCC). Methods The expression of circ_0003998 and microRNA (miR)-218-5p and eukaryotic translation initiation factor 5A-2 (EIF5A2) mRNA was detected using quantitative real-time polymerase chain reaction. Cell viability, migration and invasion were analyzed using cell counting kit-8, colony formation and transwell assay, respectively. The levels of matrix metallopeptidase 9 (MMP-9), E-cadherin, Vimentin, N-cadherin and EIF5A2 protein were detected using western blot. The interaction between miR-218-5p and circ_0003998 or EIF5A2 was confirmed by dual-luciferase reporter assay. In vivo experiments were performed using murine xenograft models. Results Circ_0003998 was elevated in HCC tissues, DOX-resistant tissues and cells, and circ_0003998 knockdown promoted DOX-sensitivity in HCC by inhibiting resistant cell viability, migration, invasion and EMT in vitro and enhanced DOX cytotoxicity in vivo. Bioinformatics analysis revealed circ_0003998 inhibited miR-218-5p expression, which was clarified to be a target of circ_0003998, and circ_0003998 knockdown sensitized HCC cell to DOX by sponging miR-218-5p. EIF5A2 was a target of miR-218-5p, and miR-218-5p mitigated DOX resistance in HCC cells through modulating EIF5A2 expression. Additionally, circ_0003998 served as a competing endogenous RNA for miR-218-5p to regulate EIF5A2 expression. Conclusion Circ_0003998 knockdown sensitized HCC cell to DOX by regulating miR-218-5p/EIF5A2 axis, indicating new markers of poor response to DOX and potential therapeutic strategies for the chemotherapy of HCC.https://doi.org/10.1186/s13000-020-01056-1circ_0003998miR-218-5pEIF5A2HCCDoxorubicin resistance |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiaomin Li Jiefeng He Xiaojing Ren Haichao Zhao Haoliang Zhao |
spellingShingle |
Xiaomin Li Jiefeng He Xiaojing Ren Haichao Zhao Haoliang Zhao Circ_0003998 enhances doxorubicin resistance in hepatocellular carcinoma by regulating miR-218-5p/EIF5A2 pathway Diagnostic Pathology circ_0003998 miR-218-5p EIF5A2 HCC Doxorubicin resistance |
author_facet |
Xiaomin Li Jiefeng He Xiaojing Ren Haichao Zhao Haoliang Zhao |
author_sort |
Xiaomin Li |
title |
Circ_0003998 enhances doxorubicin resistance in hepatocellular carcinoma by regulating miR-218-5p/EIF5A2 pathway |
title_short |
Circ_0003998 enhances doxorubicin resistance in hepatocellular carcinoma by regulating miR-218-5p/EIF5A2 pathway |
title_full |
Circ_0003998 enhances doxorubicin resistance in hepatocellular carcinoma by regulating miR-218-5p/EIF5A2 pathway |
title_fullStr |
Circ_0003998 enhances doxorubicin resistance in hepatocellular carcinoma by regulating miR-218-5p/EIF5A2 pathway |
title_full_unstemmed |
Circ_0003998 enhances doxorubicin resistance in hepatocellular carcinoma by regulating miR-218-5p/EIF5A2 pathway |
title_sort |
circ_0003998 enhances doxorubicin resistance in hepatocellular carcinoma by regulating mir-218-5p/eif5a2 pathway |
publisher |
BMC |
series |
Diagnostic Pathology |
issn |
1746-1596 |
publishDate |
2020-12-01 |
description |
Abstract Background The involvement of circular RNAs (circRNAs) in chemoresistance of tumors has been identified. Herein, this study aims to investigate the role and the underlying mechanism of circ_0003998 in doxorubicin (DOX) resistance in hepatocellular carcinoma (HCC). Methods The expression of circ_0003998 and microRNA (miR)-218-5p and eukaryotic translation initiation factor 5A-2 (EIF5A2) mRNA was detected using quantitative real-time polymerase chain reaction. Cell viability, migration and invasion were analyzed using cell counting kit-8, colony formation and transwell assay, respectively. The levels of matrix metallopeptidase 9 (MMP-9), E-cadherin, Vimentin, N-cadherin and EIF5A2 protein were detected using western blot. The interaction between miR-218-5p and circ_0003998 or EIF5A2 was confirmed by dual-luciferase reporter assay. In vivo experiments were performed using murine xenograft models. Results Circ_0003998 was elevated in HCC tissues, DOX-resistant tissues and cells, and circ_0003998 knockdown promoted DOX-sensitivity in HCC by inhibiting resistant cell viability, migration, invasion and EMT in vitro and enhanced DOX cytotoxicity in vivo. Bioinformatics analysis revealed circ_0003998 inhibited miR-218-5p expression, which was clarified to be a target of circ_0003998, and circ_0003998 knockdown sensitized HCC cell to DOX by sponging miR-218-5p. EIF5A2 was a target of miR-218-5p, and miR-218-5p mitigated DOX resistance in HCC cells through modulating EIF5A2 expression. Additionally, circ_0003998 served as a competing endogenous RNA for miR-218-5p to regulate EIF5A2 expression. Conclusion Circ_0003998 knockdown sensitized HCC cell to DOX by regulating miR-218-5p/EIF5A2 axis, indicating new markers of poor response to DOX and potential therapeutic strategies for the chemotherapy of HCC. |
topic |
circ_0003998 miR-218-5p EIF5A2 HCC Doxorubicin resistance |
url |
https://doi.org/10.1186/s13000-020-01056-1 |
work_keys_str_mv |
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