Long noncoding RNA lnc-LOC645166 promotes adriamycin resistance via NF-κB/GATA3 axis in breast cancer.

Ruinian Zheng,Shunhuan Lin,Huiling Yuan,Yuting Liao,Ou Huang,Chun Liu,Jun Jia,Weibiao Ye,Ling Guan,Kejun Liu

doi:10.18632/aging.103012

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.

Highlights

Breast cancer is one of the most common cancers diagnosed in women
We identified the long noncoding RNAs (lncRNAs) 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
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

Summary

Introduction

Breast cancer is one of the most common cancers diagnosed in women. Breast cancer can occur in both men and women, but is far more common in women, making breast cancer the number one cause of death in women diagnosed with a cancer-related disease worldwide [1]. Profound advances have been achieved, the survival rate of patients with breast cancer remains unsatisfactory. Chemotherapy is the standard treatment option for advanced breast cancer [2]; drug resistance has become the primary obstacle for breast carcinoma therapy [3]. ADR efficiently reduces the recurrence and mortality in breast cancer patients. Several patients have failed to respond to treatments with ADR, owing to an intrinsic or acquired resistance [5]. Reliable biomarkers that may predict drug responses are not currently available

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