BMC Cancer最新文献

Background: Colon cancer (CC) is a malignant cancer with high incidence and poor prognosis.Ferroptosis could induce iron-dependent accumulation of lipid peroxidation and oxidative death of cancer cells. This work aimed to elucidate the role of KAT6A, a lysine acetyltransferase, in CC development.

Methods: We collected tumor and paired non-tumor samples from patients with CC and analyzed the RNA and protein level of KAT6A using quantitative real-time PCR and immunohistochemistry (IHC) staining. We conducted KAT6A knockdown in CC cells and determined cell proliferation and ferroptosis. Cell proliferation was measured by cell counting kit-8 (CCK-8) and colony formation assay. Ferroptosis was identified by measuring the levels of lipid ROS, intracellular iron and Fe²⁺, malondialdehyde (MDA), and glutathione (GSH). The in vivo effects of KAT6A were assessed by xenograft mouse model. Protein levels of KAT6A and glutathione peroxidase 4 (GPX4) were checked by western blotting assay. The enticement of acetylation on lysine 9 of histone3 (H3K9ac) and RNA polymerase II on GPX4 gene was analyzed by chromatin immunoprecipitation (ChIP) assay.

Results: The RNA and protein level of KAT6A is notably higher in tumor tissues compared with the non-tumor sections. Depletion of KAT6A suppressed in vitro and in vivo CC cell growth. Overexpression of KAT6A reversed the erastin-induced CC cell death. knockdown of KAT6A significantly elevated the intracellular level of MDA, induced accumulation of total iron, Fe²⁺ and lipid ROS, and suppressed the level of GSH. The knockdown of KAT6A caused a decrease in the expression of GPX4 and enrichment of H3K9ac on GPX4 gene.

Conclusion: KAT6A promotes the proliferation of CC cells and suppresses ferroptosis via epigenetic regulation of GPX4. Our work presented KAT6A as a potential diagnostic and therapeutic target for treatment CC.

Background: Anoikis, a form of cell death triggered by detachment from cell-cell contact, is closely associated with tumor invasion and metastasis. After LUAD has metastasized to the brain, the prognosis is extremely poor. This study aims to investigate the role of Anoikis-related genes (ARGs) in the progression of lung cancer brain metastasis.

Methods: We analyzed six lung cancer and six brain metastasis samples from a single-cell RNA sequencing (scRNA-seq) dataset. Potential molecular mechanisms were explored through cell communication and transcription factor regulation. AddModuleScore was applied to score cell types based on 338 ARGs. A cluster with the most significant score difference between the lung tumor (tumor group) and brain metastasis (mBrain group) was selected for pseudotime analysis. Epithelial differentiation genes were identified and intersected with ARGs. Using bulk RNA sequencing and patient survival data, a prognostic model was developed. Clinical samples were collected to validate differential expression between the two groups. ARGs associated with metastasis were knocked down to confirm their molecular functions.

Results: Epithelial cells exhibited the greatest difference between the two groups in terms of AddModuleScore and cell proportions. Cell communication analysis revealed strong enrichment of VEGF signaling. Transcription factor analysis identified distinct regulatory networks. A prognostic model based on bulk RNA data was constructed, with key genes including ITGA2, ITGA3, CD44, and BIRC3. ARGs were significantly associated with immune infiltration and immune checkpoint modulation. Clinical validation revealed that CD44 was significantly overexpressed in brain metastasis tissues. Knocking down CD44 significantly impaired cell proliferation, migration, and invasion.

Conclusion: Our findings indicate that epithelial cells undergo profound changes during lung cancer brain metastasis. ARGs, particularly CD44, play a critical role in this process and have prognostic significance for lung cancer brain metastasis.