American Association for Cancer Research
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00085472can211155-sup-263991_3_supp_7503369_r1w19v.pdf (3.95 MB)

Supplementary Data from Analysis of the Estrogen Receptor-Associated LncRNA Landscape Identifies a Role for ERLC1 in Breast Cancer Progression

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journal contribution
posted on 2023-03-31, 05:02 authored by Hui Yuan, Linlin Yan, Mingming Wu, Yinzhong Shang, Qianying Guo, Xin Ma, Xiao Zhang, Yong Zhu, Zhengsheng Wu, Peter E. Lobie, Tao Zhu

Supplementary table S1 lists 22 breast cancer and ERα associated lncRNAs. Supplementary table S2 lists all primers sequences, oligonucleotides sequences, and probes sequences used in this study. Supplementary table S3 shows the information of antibodies used in this study. Supplementary table S4 shows the sequence of ERLC1 in the overexpression system. Supplementary figure S1 shows that ERLC1 is screened as an ERα-regulated gene in breast cancer. Supplementary figure S2 shows that ERLC1 is an oncogene in MCF-7 and T47D cells. Supplementary figure S3 shows that ERLC1 regulates anti-estrogen sensitivity and tamoxifen resistance in T47D cells. Supplementary figure S4 shows that miR-129 is a tumor suppressor gene and ERLC1 expression is negatively correlated with miR-129 levels. Supplementary figure S5 shows that ERLC1 promotes ESR1 expression through sequestration of miR-129. Supplementary figure S6 shows that ERLC1 and FXR1 form a functional complex stabilizing ESR1 mRNA. Supplementary figure S7 shows that ESR1 mutants did not interact with ERLC1 promoter. Supplementary figure S8 shows that ERLC1 depletion reduces resistance to fulvestrant and palbociclib in MCF-7 TamR cells.

Funding

National Key Scientific Program of China

National Natural Science Foundation of China

Shenzhen Key Laboratory of Innovative Oncotherapeutics

Guangdong Basic and Applied Basic Research Foundation

Overseas Research Cooperation Project

History

ARTICLE ABSTRACT

Estrogen receptor alpha (ERα) plays a vital role in the development of normal breast tissue and in breast cancer. By cross-analyzing The Cancer Genome Atlas (TCGA) database, ERα-regulated long noncoding RNA 1 (ERLC1) was identified as a long noncoding RNA exhibiting a strong association with ERα signaling and high specificity of expression in breast tissue. ERLC1 was transcriptionally activated by ERα, and ERLC1 stabilized the ESR1 transcript by sequestering miR-129 and tethering FXR1 to maintain a positive feedback loop that potentiated ERα signaling. ERLC1 was elevated in tamoxifen-resistant breast cancer cells, where ERLC1 depletion restored sensitivity to tamoxifen and increased the efficacy of palbociclib or fulvestrant therapy. Collectively, these data warrant further investigation of ERLC1 as a modulator of therapeutic response and potential therapeutic target in ER+ breast cancer. This study identifies an estrogen-regulated lncRNA and the mechanism by which it positively regulates ERα activity, demonstrating a feedback loop that can promote resistance to antiestrogen therapies in ER+ breast cancer.