Kundu Subhadip, Jit Bimal Prasad, Sharma Ashok
Laboratory of Chromatin and Cancer Epigenetics, Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, 110029, India.
National Cancer Institute, All India Institute of Medical Sciences, Jhajjar, Haryana, India.
Mamm Genome. 2025 Mar;36(1):230-249. doi: 10.1007/s00335-024-10086-9. Epub 2024 Nov 27.
Lamins play a crucial role in maintaining nuclear structure and function. Our study investigates the expression patterns and clinical implications of B-type lamins with a special focus on lamin B2 across various cancer types using comprehensive RNA sequencing datasets. We found that high expression levels of lamin B1 and lamin B2 are associated with decreased overall and disease-free survival in cancer. This association is further pronounced when both lamins are co-expressed, indicating a compounded negative impact on patient prognosis. Additionally, we highlighted the relationship between B-type lamins and the tumor microenvironment. Lamin B1 mRNA expression shows a strong positive correlation with activated CD4 T-cells and type 2 T-helper cells (Th2), suggesting its role in immune cell infiltration and response within tumors. Lamin B2 expression also correlates moderately with these immune cells, indicating a potential but lesser role in modulating the immune landscape. Notably, the epigenetic state of lamin B1 significantly affects the tumor microenvironment, suggesting a dual role in structural integrity and immune modulation. We have identified 9 lamin B2 interacting proteins that are co-expressed with B-type lamins in cancerous conditions and modulate cytokinesis and cell division pathways during tumorigenesis. Furthermore, we have identified specific molecular targets of B-type lamins that co-express with them in a range of human cancers and are potentially involved in dysregulating chromosome segregation and mRNA binding. Overexpression of these targets alongside B-type lamins correlates with poor prognosis in multiple cancers. These findings underscore the potential of B-type lamins as biomarkers for poor prognosis and as targets for cancer therapies.
核纤层蛋白在维持细胞核结构和功能方面发挥着关键作用。我们的研究利用全面的RNA测序数据集，研究了B型核纤层蛋白的表达模式及其临床意义，特别关注了多种癌症类型中的核纤层蛋白B2。我们发现，核纤层蛋白B1和核纤层蛋白B2的高表达水平与癌症患者的总生存期和无病生存期降低有关。当这两种核纤层蛋白共同表达时，这种关联更为明显，表明对患者预后有复合负面影响。此外，我们强调了B型核纤层蛋白与肿瘤微环境之间的关系。核纤层蛋白B1的mRNA表达与活化的CD4 T细胞和2型辅助性T细胞（Th2）呈强正相关，表明其在肿瘤内免疫细胞浸润和反应中的作用。核纤层蛋白B2的表达也与这些免疫细胞有中度相关性，表明其在调节免疫格局方面有潜在但较小的作用。值得注意的是，核纤层蛋白B1的表观遗传状态显著影响肿瘤微环境，表明其在结构完整性和免疫调节方面具有双重作用。我们已经鉴定出9种与B型核纤层蛋白在癌症状态下共同表达并在肿瘤发生过程中调节胞质分裂和细胞分裂途径的核纤层蛋白B2相互作用蛋白。此外，我们已经鉴定出B型核纤层蛋白在一系列人类癌症中与其共同表达且可能参与染色体分离失调和mRNA结合异常调节的特定分子靶点。这些靶点与B型核纤层蛋白一起过表达与多种癌症的不良预后相关。这些发现强调了B型核纤层蛋白作为不良预后生物标志物和癌症治疗靶点的潜力。
