Research Paper Volume 12, Issue 10 pp 8893—8912
Long noncoding RNA lnc-LOC645166 promotes adriamycin resistance via NF-κB/GATA3 axis in breast cancer
- 1 Department of Oncology, Affiliated Dongguan People's Hospital, Southern Medical University, Dongguan 523000, Guangdong Province, P.R. China
- 2 Clinical Research Center, Affiliated Dongguan People's Hospital, Southern Medical University, Dongguan 523000, Guangdong Province, P.R. China
- 3 Department of Galactophore, Affiliated Dongguan People's Hospital, Southern Medical University, Dongguan 523000, Guangdong Province, P.R. China
- 4 Department of Pathology, Affiliated Dongguan People's Hospital, Southern Medical University, Dongguan 523000, Guangdong Province, P.R. China
- 5 Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
Received: September 5, 2019 Accepted: March 2, 2020 Published: May 27, 2020
https://doi.org/10.18632/aging.103012How to Cite
Copyright © 2020 Zheng et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Chemoresistance remains a significant obstacle for effective adriamycin (ADR) treatment in breast cancer. Recent efforts have revealed that long noncoding RNAs (lncRNAs) play a crucial role in cancer biology, including chemoresistance. We identified the lncRNA LOC645166 was upregulated in adriamycin resistant-breast cancer cells by Microarray analysis, which was further confirmed in the tissues of nonresponsive patients by reverse transcription-quantitative polymerase chain reaction (RT–qPCR), western blotting, and immunohistochemical assays. Downregulation of lncRNA LOC645166 increased cell sensitivity to adriamycin both in vitro and in vivo. In contrast, upregulation of lncRNA LOC645166 strengthened the tolerance of breast cancer cells to adriamycin. Chromatin immunoprecipitation (ChIP) and RNA binding protein immunoprecipitation (RIP) demonstrated that lncRNA LOC645166 could increase the expression of GATA binding protein 3 (GATA3) via binding with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), leading to the activation of STAT3 and promoting chemoresistance in breast cancer. Together, the present study suggested that lncRNA LOC645166 mediated adriamycin chemoresistance in breast cancer by regulating GATA3 via NF-κB.
Abbreviations
ADR: Adriamycin; lncRNAs: long noncoding RNAs; ChIP: Chromatin immunoprecipitation; RIP: RNA binding protein immunoprecipitation; 231: MDA-MB-231; FBS: Fetal bovine serum; IHC: Immuno-histochemistry; sh-RNA: short hairpin RNA.