Project description:Breast cancer (BC) is the most prevailing type of cancer among women in the world. ERα protein, which is transcribed and translated by estrogen receptor gene ESR1, is one of the marker molecules for clinical classification of BC. However, whether circRNAs specifically expressed in hormone receptor-positive BC play a role which is independent of ERα (estrogen receptor alpha) protein activity and signaling pathways is unknown. Whether these circRNAs could impinge on the sensitivity of ER+ BC cells to the endocrine therapy and targeted drug therapy is also unexplored.By screening circRNAs involved in estrogen receptor (ER) signaling, circESR1 was identified as a circRNA exhibiting high specificity of expression in ER+ breast cancer. Our studies elucidate a novel signaling complex centering around circESR1 and HNRNPAB in ER+ breast cancer and suggest that circESR1 might represent a potential therapeutic target for this disease.
Project description:The immune system's role in estrogen receptor (ER)-positive breast cancer is poorly understood. A population-based cohort of 428 breast cancer patients with clinical and molecular data was analyzed to assess how immune biomarkers can inform treatment decisions. Tumor-intrinsic immune responsiveness and local immune infiltration were quantified, and epithelial cell states were derived using EcoTyper. The interaction between ProliferativeIndex and Immunescore predicted risk of local recurrence in ER-positive tumors (HR 0.56, 95% CI 0.36-0.88, p=0.012). EcoTyper identified two epithelial cell states, S04 and S05, with distinct immunomodulatory properties. S04 tumors showed higher proliferation, enrichment for M1 macrophages, CD8 effector T-cells, and plasma cells, alongside hypomethylation of immune-related pathways and hypermethylation of the PI3K signaling pathway. In contrast, S05-enriched tumors were associated with fibroblast activation, immune exclusion, and enrichment for glycosylation-related pathways. These findings suggest that epithelial cell states shape immune responsiveness in ER-positive breast cancer and may inform biomarker-driven treatment strategies.
Project description:Estrogen receptor (ER)-positive MCF7 breast cancer cells were treated with siRNAs targeting CHRNA5, TP53, or both in combination to investigate TP53-dependent and independent transcriptional responses to CHRNA5 knockdown. Previous studies have shown that CHRNA5 silencing induces cell death via TP53 pathway activation. To further elucidate the molecular mechanisms underlying this effect, we performed RNA sequencing following 72-hour treatments with siCHRNA5, siTP53, and their combination, alongside appropriate siRNA controls. This dataset provides a valuable resource for understanding the role of CHRNA5 in ER-positive breast cancer and its interaction with TP53 signaling, with implications for therapeutic targeting strategies.
Project description:RanBP2 type and C3HC4 type zinc finger containing protein 1 (RBCK1,) is a 58 kDa protein containing N-terminal ubiquitin like (UBL) domain, npl4 type zinc finger (NZF) domain and catalytic carbon terminal RBR domain. It is known that it has abnormal expression in tumors, making it a valuable diagnostic marker and drug target. A large number of studies have confirmed that in ER positive breast cancer, about 25%-40% of the tumor showed a visible hypoxia area. Under hypoxia, tumor cells can activate HIF1 pathway and widely activate the expression of downstream genes. Hypoxia inducible factor HIF-1 is composed of HIF-1α and HIF-1β Two subunits, The protein level of HIF-1α is precisely regulated by oxygen concentration. Here, we report RBCK1, a RING family ubiquitin ligase that regulates HIF1α, promoting ER positive breast cancer growth and inhibiting apoptosis. Deletion of RBCK1 inhibits ER positive breast cancer growth and promotes cell death. RNA sequencing analysis showed that in ER positive breast cancer, RBCK1 may be an important modifier of HIF1α signal pathway. Further experiments showed that RBCK1 and HIF1α Interacts and inhibits HIF1α polyubiquitination to inhibit HIF1α degradation in ER positive breast cancer cells. These finding reveals a novel direct HIF1α regulator and a potential therapeutic target for ER positive breast cancer.
