Circ_0006528 Contributes to Paclitaxel Resistance of Breast Cancer Cells by Regulating miR-1299/CDK8 Axis
Guoqi Liu,1 Zhenxing Zhang,1 Qing Song,2 Yanling Guo,1 Puqiang Bao,1 Huifeng Shui1 1Department of Integrated Traditional Chinese and Western Medicine in Oncology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, People’s Republic of China; 2Department of Oncology and H...
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doaj-50c941d6cf104e709d0a58aa3ea95b192020-11-25T02:42:03ZengDove Medical PressOncoTargets and Therapy1178-69302020-09-01Volume 139497951157335Circ_0006528 Contributes to Paclitaxel Resistance of Breast Cancer Cells by Regulating miR-1299/CDK8 AxisLiu GZhang ZSong QGuo YBao PShui HGuoqi Liu,1 Zhenxing Zhang,1 Qing Song,2 Yanling Guo,1 Puqiang Bao,1 Huifeng Shui1 1Department of Integrated Traditional Chinese and Western Medicine in Oncology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, People’s Republic of China; 2Department of Oncology and Hematology, No. 989 Hospital of Joint Logistics Support Force of Chinese People’s Liberation Army, Pingdingshan, People’s Republic of ChinaCorrespondence: Huifeng ShuiDepartment of Integrated Traditional Chinese and Western Medicine in Oncology, Luoyang Central Hospital Affiliated to Zhengzhou University, No. 288 Zhongzhou Middle Road, Luoyang 471009, Henan, People’s Republic of ChinaTel +86-379-63892209Email dskvmf@163.comBackground: Circular RNAs (circRNAs) have been reported to be involved in regulating the development of breast cancer. Paclitaxel (PTX) can be used for the chemotherapy of breast cancer. The study aimed to explore the role and mechanism of circ_0006528 in PTX-resistant breast cancer progression.Methods: The levels of circ_0006528, microRNA-1299 (miR-1299) and cyclin-dependent kinase 8 (CDK8) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). RNase R treatment was used to confirm that the circ_0006528 was a circular RNA. PTX resistance and cell proliferation were determined by Cell counting kit-8 (CCK-8) assay. Cell apoptosis, migration and invasion were analyzed by flow cytometry and Transwell assays, respectively. The levels of all proteins were examined by Western blot. The interaction between circ_0006528 and miR-1299 or CDK8 was predicted by online database confirmed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft mice model was constructed to reveal the role of circ_0006528 on tumor growth in vivo.Results: Circ_0006528 was significantly up-regulated and miR-1299 was down-regulated in PTX-resistant breast cancer tissues and cells compared with control groups. CDK8 protein expression was dramatically upregulated in PTX-resistant breast cancer tissues and cells as compared to control groups. Loss-of-function experiments revealed that circ_0006528 knockdown decreased IC50 value of PTX and restrained proliferation, migration, invasion and autophagy, whereas induced apoptosis of PTX-resistant breast cancer cells in vitro. The inhibitory effects of sh-circ_0006528 on the progression of PTX-resistant breast cancer cells were reversed by decreasing miR-1299 or increasing CDK8 expression. Furthermore, circ_0006528 could modulate CDK8 expression by sponging miR-1299. Circ_0006528 silencing impeded the growth of PTX-resistant tumors by regulating miR-1299/CDK8 axis in vivo.Conclusion: Circ_0006528 partially contributed to PTX resistance of breast cancer cells through up-regulating CDK8 expression by sponging miR-1299.Keywords: breast cancer, paclitaxel resistance, circ_0006528, miR-1299, CDK8https://www.dovepress.com/circ0006528-contributes-to-paclitaxel-resistance-of-breast-cancer-cell-peer-reviewed-article-OTTbreast cancerpaclitaxel resistancecirc_0006528mir-1299cdk8 |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Liu G Zhang Z Song Q Guo Y Bao P Shui H |
spellingShingle |
Liu G Zhang Z Song Q Guo Y Bao P Shui H Circ_0006528 Contributes to Paclitaxel Resistance of Breast Cancer Cells by Regulating miR-1299/CDK8 Axis OncoTargets and Therapy breast cancer paclitaxel resistance circ_0006528 mir-1299 cdk8 |
author_facet |
Liu G Zhang Z Song Q Guo Y Bao P Shui H |
author_sort |
Liu G |
title |
Circ_0006528 Contributes to Paclitaxel Resistance of Breast Cancer Cells by Regulating miR-1299/CDK8 Axis |
title_short |
Circ_0006528 Contributes to Paclitaxel Resistance of Breast Cancer Cells by Regulating miR-1299/CDK8 Axis |
title_full |
Circ_0006528 Contributes to Paclitaxel Resistance of Breast Cancer Cells by Regulating miR-1299/CDK8 Axis |
title_fullStr |
Circ_0006528 Contributes to Paclitaxel Resistance of Breast Cancer Cells by Regulating miR-1299/CDK8 Axis |
title_full_unstemmed |
Circ_0006528 Contributes to Paclitaxel Resistance of Breast Cancer Cells by Regulating miR-1299/CDK8 Axis |
title_sort |
circ_0006528 contributes to paclitaxel resistance of breast cancer cells by regulating mir-1299/cdk8 axis |
publisher |
Dove Medical Press |
series |
OncoTargets and Therapy |
issn |
1178-6930 |
publishDate |
2020-09-01 |
description |
Guoqi Liu,1 Zhenxing Zhang,1 Qing Song,2 Yanling Guo,1 Puqiang Bao,1 Huifeng Shui1 1Department of Integrated Traditional Chinese and Western Medicine in Oncology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, People’s Republic of China; 2Department of Oncology and Hematology, No. 989 Hospital of Joint Logistics Support Force of Chinese People’s Liberation Army, Pingdingshan, People’s Republic of ChinaCorrespondence: Huifeng ShuiDepartment of Integrated Traditional Chinese and Western Medicine in Oncology, Luoyang Central Hospital Affiliated to Zhengzhou University, No. 288 Zhongzhou Middle Road, Luoyang 471009, Henan, People’s Republic of ChinaTel +86-379-63892209Email dskvmf@163.comBackground: Circular RNAs (circRNAs) have been reported to be involved in regulating the development of breast cancer. Paclitaxel (PTX) can be used for the chemotherapy of breast cancer. The study aimed to explore the role and mechanism of circ_0006528 in PTX-resistant breast cancer progression.Methods: The levels of circ_0006528, microRNA-1299 (miR-1299) and cyclin-dependent kinase 8 (CDK8) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). RNase R treatment was used to confirm that the circ_0006528 was a circular RNA. PTX resistance and cell proliferation were determined by Cell counting kit-8 (CCK-8) assay. Cell apoptosis, migration and invasion were analyzed by flow cytometry and Transwell assays, respectively. The levels of all proteins were examined by Western blot. The interaction between circ_0006528 and miR-1299 or CDK8 was predicted by online database confirmed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft mice model was constructed to reveal the role of circ_0006528 on tumor growth in vivo.Results: Circ_0006528 was significantly up-regulated and miR-1299 was down-regulated in PTX-resistant breast cancer tissues and cells compared with control groups. CDK8 protein expression was dramatically upregulated in PTX-resistant breast cancer tissues and cells as compared to control groups. Loss-of-function experiments revealed that circ_0006528 knockdown decreased IC50 value of PTX and restrained proliferation, migration, invasion and autophagy, whereas induced apoptosis of PTX-resistant breast cancer cells in vitro. The inhibitory effects of sh-circ_0006528 on the progression of PTX-resistant breast cancer cells were reversed by decreasing miR-1299 or increasing CDK8 expression. Furthermore, circ_0006528 could modulate CDK8 expression by sponging miR-1299. Circ_0006528 silencing impeded the growth of PTX-resistant tumors by regulating miR-1299/CDK8 axis in vivo.Conclusion: Circ_0006528 partially contributed to PTX resistance of breast cancer cells through up-regulating CDK8 expression by sponging miR-1299.Keywords: breast cancer, paclitaxel resistance, circ_0006528, miR-1299, CDK8 |
topic |
breast cancer paclitaxel resistance circ_0006528 mir-1299 cdk8 |
url |
https://www.dovepress.com/circ0006528-contributes-to-paclitaxel-resistance-of-breast-cancer-cell-peer-reviewed-article-OTT |
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