Long non-coding RNA H19 regulates proliferation and doxorubicin resistance in MCF-7 cells by targeting PARP1

Chemoresistance is a major obstacle to effective breast cancer chemotherapy. However, the underlying molecular mechanisms remain unclear. The long noncoding RNA H19 (H19) is involved in various stages of tumorigenesis, however, its role in doxorubicin resistance remains unknown. The goal of this stu...

Full description

Bibliographic Details
Main Authors: Yu Wang, Peihong Zhou, Ping Li, Fengxia Yang, Xue-qiang Gao
Format: Article
Language:English
Published: Taylor & Francis Group 2020-01-01
Series:Bioengineered
Subjects:
Online Access:http://dx.doi.org/10.1080/21655979.2020.1761512
id doaj-32334539456f41f8bdc2824c75ecfb31
record_format Article
spelling doaj-32334539456f41f8bdc2824c75ecfb312021-06-02T08:43:40ZengTaylor & Francis GroupBioengineered2165-59792165-59872020-01-0111153654610.1080/21655979.2020.17615121761512Long non-coding RNA H19 regulates proliferation and doxorubicin resistance in MCF-7 cells by targeting PARP1Yu Wang0Peihong Zhou1Ping Li2Fengxia Yang3Xue-qiang Gao4The Affiliated Hospital of Qingdao UniversityThe Affiliated Hospital of Qingdao UniversityThe Affiliated Hospital of Qingdao UniversityThe Affiliated Hospital of Qingdao UniversityThe Affiliated Hospital of Qingdao UniversityChemoresistance is a major obstacle to effective breast cancer chemotherapy. However, the underlying molecular mechanisms remain unclear. The long noncoding RNA H19 (H19) is involved in various stages of tumorigenesis, however, its role in doxorubicin resistance remains unknown. The goal of this study was to evaluate the role of H19 in the development of doxorubicin-resistant breast cancer. Quantitative real-time PCR (qRT-PCR) analyzed H19 expression in chemotherapy-resistant and sensitive breast cancer tissues. Both knockdown and overexpression of H19 were used to assess the sensitivity to doxorubicin in breast cancer cells in vitro and in vivo. qRT-PCR and Western blot were used to explore the doxorubicin resistance mechanism of H19. We observed that the H19 expression was significantly upregulated in chemotherapy-resistant breast cancer tissues and doxorubicin-resistant breast cancer cell lines. Knockdown of H19 enhanced the sensitivity to doxorubicin both in vitro and in vivo. While H19 overexpression developed doxorubicin-resistant in breast cancer cells both in vitro and in vivo. Furthermore, it was revealed that H19 negatively regulated PARP1 expression in breast cancer cells following doxorubicin treatment. Knockdown of H19 sensitized breast cancer cells to doxorubicin by promoting PARP1 upregulation. H19 overexpression could recapitulate doxorubicin resistance by PARP1 downregulation. Our findings revealed that H19 plays a leading role in breast cancer chemoresistance development, mediated mainly through a H19-PARP1 pathway.http://dx.doi.org/10.1080/21655979.2020.1761512breast cancerchemotherapydoxorubicinlncrna h19parp1
collection DOAJ
language English
format Article
sources DOAJ
author Yu Wang
Peihong Zhou
Ping Li
Fengxia Yang
Xue-qiang Gao
spellingShingle Yu Wang
Peihong Zhou
Ping Li
Fengxia Yang
Xue-qiang Gao
Long non-coding RNA H19 regulates proliferation and doxorubicin resistance in MCF-7 cells by targeting PARP1
Bioengineered
breast cancer
chemotherapy
doxorubicin
lncrna h19
parp1
author_facet Yu Wang
Peihong Zhou
Ping Li
Fengxia Yang
Xue-qiang Gao
author_sort Yu Wang
title Long non-coding RNA H19 regulates proliferation and doxorubicin resistance in MCF-7 cells by targeting PARP1
title_short Long non-coding RNA H19 regulates proliferation and doxorubicin resistance in MCF-7 cells by targeting PARP1
title_full Long non-coding RNA H19 regulates proliferation and doxorubicin resistance in MCF-7 cells by targeting PARP1
title_fullStr Long non-coding RNA H19 regulates proliferation and doxorubicin resistance in MCF-7 cells by targeting PARP1
title_full_unstemmed Long non-coding RNA H19 regulates proliferation and doxorubicin resistance in MCF-7 cells by targeting PARP1
title_sort long non-coding rna h19 regulates proliferation and doxorubicin resistance in mcf-7 cells by targeting parp1
publisher Taylor & Francis Group
series Bioengineered
issn 2165-5979
2165-5987
publishDate 2020-01-01
description Chemoresistance is a major obstacle to effective breast cancer chemotherapy. However, the underlying molecular mechanisms remain unclear. The long noncoding RNA H19 (H19) is involved in various stages of tumorigenesis, however, its role in doxorubicin resistance remains unknown. The goal of this study was to evaluate the role of H19 in the development of doxorubicin-resistant breast cancer. Quantitative real-time PCR (qRT-PCR) analyzed H19 expression in chemotherapy-resistant and sensitive breast cancer tissues. Both knockdown and overexpression of H19 were used to assess the sensitivity to doxorubicin in breast cancer cells in vitro and in vivo. qRT-PCR and Western blot were used to explore the doxorubicin resistance mechanism of H19. We observed that the H19 expression was significantly upregulated in chemotherapy-resistant breast cancer tissues and doxorubicin-resistant breast cancer cell lines. Knockdown of H19 enhanced the sensitivity to doxorubicin both in vitro and in vivo. While H19 overexpression developed doxorubicin-resistant in breast cancer cells both in vitro and in vivo. Furthermore, it was revealed that H19 negatively regulated PARP1 expression in breast cancer cells following doxorubicin treatment. Knockdown of H19 sensitized breast cancer cells to doxorubicin by promoting PARP1 upregulation. H19 overexpression could recapitulate doxorubicin resistance by PARP1 downregulation. Our findings revealed that H19 plays a leading role in breast cancer chemoresistance development, mediated mainly through a H19-PARP1 pathway.
topic breast cancer
chemotherapy
doxorubicin
lncrna h19
parp1
url http://dx.doi.org/10.1080/21655979.2020.1761512
work_keys_str_mv AT yuwang longnoncodingrnah19regulatesproliferationanddoxorubicinresistanceinmcf7cellsbytargetingparp1
AT peihongzhou longnoncodingrnah19regulatesproliferationanddoxorubicinresistanceinmcf7cellsbytargetingparp1
AT pingli longnoncodingrnah19regulatesproliferationanddoxorubicinresistanceinmcf7cellsbytargetingparp1
AT fengxiayang longnoncodingrnah19regulatesproliferationanddoxorubicinresistanceinmcf7cellsbytargetingparp1
AT xueqianggao longnoncodingrnah19regulatesproliferationanddoxorubicinresistanceinmcf7cellsbytargetingparp1
_version_ 1721406327904796672