Abstract
BackgroundTamoxifen and fulvestrant, both approved for endocrine therapy, have remarkably increased the prognosis of hormone receptor-positive breast cancer patients. However, acquired resistance to endocrine therapy greatly reduces its clinical efficacy. Accumulating evidence suggests a pivotal role of non-coding RNAs (ncRNAs) in breast cancer endocrine resistance, but the specific functions of ncRNAs in tamoxifen and fulvestrant resistance remain largely unknown.MethodsMicroarray analysis was performed for endocrine therapy sensitive (MCF-7), tamoxifen-resistant (LCC2), and dual tamoxifen and fulvestrant-resistant (LCC9) breast cancer cells. Gene ontology and pathway analysis were conducted for functional prediction of the unannotated differentially expressed ncRNAs. Competing endogenous RNA regulatory networks were constructed.ResultsWe discovered a total of 3,129 long non-coding RNAs (lncRNAs), 13,556 circular RNAs (circRNAs), 132 microRNAs, and 3358 mRNAs that were significantly differentially expressed. We constructed co-expression networks for lncRNA-mRNA, circRNA-mRNA, and microRNA-mRNA. In addition, we established lncRNA-microRNA-mRNA and circRNA-microRNA-mRNA regulatory networks to depict ncRNA crosstalk and transcriptomic regulation of endocrine resistance.ConclusionsOur study delineates a comprehensive profiling of ncRNAs in tamoxifen and fulvestrant resistant breast cancer cells, which enriches our understanding of endocrine resistance and sheds new light on identifying novel endocrine resistance biomarkers and potential therapeutic targets to overcome endocrine resistance.
Highlights
Breast cancer remains one of the leading causes for cancer-related mortality in women, with an incidence rate of 124.7 per 100,000 population and a mortality rate of 20.6 per 100,000 population [1]
Different RNA species, such as long non-coding RNA circRNA (lncRNA), circRNA, and mRNA can compete in binding microRNA, constituting a competing endogenous RNA network, in which gene expression is coordinately regulated by different non-coding RNAs (ncRNAs) [6]
We validated that MCF-7 was sensitive to both tamoxifen and fulvestrant; LCC2 was only sensitive to fulvestrant; LCC9 was resistant to both drugs
Summary
Breast cancer remains one of the leading causes for cancer-related mortality in women, with an incidence rate of 124.7 per 100,000 population and a mortality rate of 20.6 per 100,000 population [1]. Different RNA species, such as lncRNA, circRNA, and mRNA can compete in binding microRNA, constituting a competing endogenous RNA (ceRNA) network, in which gene expression is coordinately regulated by different ncRNAs [6]. Tamoxifen and fulvestrant, both approved for endocrine therapy, have remarkably increased the prognosis of hormone receptor-positive breast cancer patients. Accumulating evidence suggests a pivotal role of non-coding RNAs (ncRNAs) in breast cancer endocrine resistance, but the specific functions of ncRNAs in tamoxifen and fulvestrant resistance remain largely unknown
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