Supplementary Figures 1-5. Supplementary Figure 1. ERINA is a nuclear lncRNA that affects the survival and cell proliferation marker of ER-positive breast cancer patients. Supplementary Figure 2. ERINA knockdown and overexpression efficiency and the morphology change of knockdown cells. Supplementary Figure 3. RNA sequencing analysis showed the number of up-regulated genes and downregulated genes in T47D cells. Supplementary Figure 4. GSEA analysis revealed ERINA played a crucial role in RB1-involved pathway. Supplementary Figure 5. ChIP-seq analysis reveals the binding of RNA polymerase II within the promoter region of ERINA. (A) Alignment of RNA polymerase II ChIP-seq in MCF7 cells. The binding peak and genomic locus are shown.
ARTICLE ABSTRACT
Resistance to therapeutic drugs is a major challenge in the treatment of cancers, including breast cancer. Long noncoding RNAs (lncRNA) are known to have diverse physiologic and pathophysiologic functions, including in cancer. In searching for lncRNA responsible for cancer drug resistance, we identified an intergenic lncRNA ERINA (estrogen inducible lncRNA) as a novel lncRNA highly expressed in multiple cancer types, especially in estrogen receptor–positive (ER+) breast cancers. Expression of ERINA was inversely correlated with survival of patients with ER+ breast cancer and sensitivity to CDK inhibitor in breast cancer cell lines. Functional characterization established ERINA as an oncogenic lncRNA, as knockdown of ERINA in breast cancer cells inhibited cell-cycle progression and tumor cell proliferation in vitro and xenograft tumor growth in vivo. In contrast, overexpression of ERINA promoted cell growth and cell-cycle progression. ERINA promoted cell-cycle progression by interacting with the E2F transcription factor 1 (E2F1), which prevents the binding of E2F1 to the tumor suppressor retinoblastoma protein 1 (RB1). ERINA also functioned as an estrogen and ER-responsive gene, and an intronic ER-binding site was identified as an enhancer that mediates the transactivation of ERINA. In summary, ERINA is an estrogen-responsive oncogenic lncRNA that may serve as a novel biomarker and potential therapeutic target in breast cancer.
These findings identify ERINA as an estrogen-responsive, oncogenic lncRNA, whose elevated expression may contribute to drug resistance and poor survival of patients with ER+ breast cancer.
