SPACA6P-AS: a trailblazer in breast cancer pathobiology and therapeutics.

OBJECTIVE: The primary objective of this investigation is to delve into the involvement of the long noncoding RNA (lncRNA) SPACA6P-AS in breast cancer (BC) development, focusing on its expression pattern, association with clinical-pathological features, impact on prognosis, as well as its molecular and immunological implications. METHODS: Bioinformatics analysis was conducted utilizing RNA sequencing data of 1083 BC patients from the TCGA database. Functional exploration of SPACA6P-AS was carried out through the construction of survival curves, GO and KEGG enrichment analysis, and single-sample gene set enrichment analysis (ssGSEA). Furthermore, its functionality was validated through in vitro cell experiments and in vivo nude mouse model experiments. RESULTS: SPACA6P-AS showed a remarkable increase in expression levels in BC tissues (p < 0.001) and demonstrated a close relationship to poor prognosis (overall survival HR = 1.616, progression-free interval HR = 1.40, disease-specific survival HR = 1.54). Enrichment analysis revealed that SPACA6P-AS could impact biological functions such as protease regulation, endopeptidase inhibitor activity, taste receptor activity, taste transduction, and maturity-onset diabetes of the young pathway. ssGSEA analysis indicated a negative correlation between SPACA6P-AS expression and immune cell infiltration like dendritic cells and neutrophils, while a positive correlation was observed with central memory T cells and T helper 2 cells. Results from in vitro and in vivo experiments illustrated that silencing SPACA6P-AS significantly inhibited the proliferation, migration, and invasion capabilities of BC cells. In vitro experiments also highlighted that dendritic cells with silenced SPACA6P-AS exhibited enhanced capabilities in promoting the proliferation of autologous CD3 + T cells and cytokine secretion. These discoveries elucidate the potential multifaceted roles of SPACA6P-AS in BC, including its potential involvement in modulating immune cell infiltration in the tumor microenvironment. CONCLUSION: The high expression of lncRNA SPACA6P-AS in BC is closely linked to poor prognosis and may facilitate tumor progression by influencing specific biological processes, signaling pathways, and the immune microenvironment. The regulatory role of SPACA6P-AS positions it as a prospective biomarker and target for therapeutic approaches for BC diagnosis and intervention.

Inducing ferroptosis has the potential to overcome therapy resistance in breast cancer.

Breast cancer is the most common type of malignancy among women. Due to the iron-dependent character of breast cancer cells, they are more sensitive to ferroptosis compared to normal cells. It is possible to reverse tumor resistance by inducing ferroptosis in breast cancer cells, thereby improving tumor treatment outcomes. Ferroptosis is highly dependent on the balance of oxidative and antioxidant status. When ferroptosis occurs, intracellular iron levels are significantly increased, leading to increased membrane lipid peroxidation and ultimately triggering ferroptosis. Ferroptotic death is a form of autophagy-associated cell death. Synergistic use of nanoparticle-loaded ferroptosis-inducer with radiotherapy and chemotherapy achieves more significant tumor suppression and inhibits the growth of breast cancer by targeting cancer tissues, enhancing the sensitivity of cells to drugs, reducing the drug resistance of cancer cells and the toxicity of drugs. In this review, we present the current status of breast cancer and the mechanisms of ferroptosis. It is hopeful for us to realize effective treatment of breast cancer through targeted ferroptosis.