The unique physiological structure of women has led to a variety of diseases that have attracted the attention of many people in recent years. Disturbances in the reproductive system microenvironment lead to the progression of various female tumours and pregnancy disorders. Numerous studies have shown that epigenetic modifications crucially influence both oogenesis and foetal development. m6A, a modification at the mRNA level, consists of three parts, namely, writers, erasers, and readers, which are involved in several biological functions, such as the nucleation and stabilisation of mRNAs, thereby regulating the development of reproductive system diseases. In this manuscript, we delineate the constituents of m6A, their biological roles, and advancements in understanding m6A within the maternal-foetal immunological context. In addition, we summarise the mechanism of m6A in gynaecological diseases and provide a new perspective for targeting m6A to delay the progression of reproductive system diseases in clinical practice.

Aging proceeds with the accumulation of senescent cells in multiple organs. These cells exhibit increased size compared to young cells, which promotes further senescence and age-related diseases. Currently, the molecular mechanism behind the maintenance of such huge cell architecture undergoing senescence remains poorly understood. Here we focus on the reorganization of actin stress fibers induced upon replicative senescence in human fibroblasts, widely used as a senescent cell model. We identified, together with our previous proteomic study, that AP2A1 (alpha 1 adaptin subunit of the adaptor protein 2) is upregulated in senescent cells along the length of enlarged stress fibers. Knockdown of AP2A1 reversed senescence-associated phenotypes, exhibiting features of cellular rejuvenation, while its overexpression in young cells advanced senescence phenotypes. Similar functions of AP2A1 were identified in UV- or drug-induced senescence and were observed in epithelial cells as well. Furthermore, we found that AP2A1 is colocalized with integrin β1, and both proteins move linearly along stress fibers. With the observations that focal adhesions are enlarged in senescent cells and that this coincides with strengthened cell adhesion to the substrate, these results suggest that senescent cells maintain their large size by reinforcing their effective anchorage through integrin β1 translocation along stress fibers. This mechanism may work efficiently in senescent cells, compared with a case relying on random diffusion of integrin β1, given the enlarged cell size and resulting increase in travel time and distance for endocytosed vesicle transportation.

Ovarian cancer (OC) is often associated with an unfavorable prognosis. Given the crucial involvement of lysosomes in tumor advancement, lysosome-related genes (LRGs) hold promise as potential therapeutic targets.

To identify differentially expressed lysosome-related genes (DE-LRGs), we performed a matching analysis between differentially expressed genes (DEGs) in OC and the pool of LRGs. Genes with prognostic significance were analyzed using multiple regression analyses to construct a prognostic risk signature. The model's efficacy was validated through survival analysis in various cohorts. We further explored the model's correlation with clinical attributes, tumor microenvironment (TME), mutational patterns, and drug sensitivity. The quantitative real-time polymerase chain reaction (qRT-PCR) validated gene expression in OC cells.

A 10-gene prognostic risk signature was established. Survival analysis confirmed its predictive accuracy across cohorts. The signature served as an independent prognostic element for OC. The high-risk and low-risk groups demonstrated notable disparities in terms of immune infiltration patterns, mutational characteristics, and sensitivity to therapeutic agents. The qRT-PCR results corroborated and validated the findings obtained from the bioinformatic analyses.

We devised a 10-LRG prognostic model linked to TME, offering insights for tailored OC treatments.

G0 arrest (G0A) is widely recognized as a crucial factor contributing to tumor relapse. The role of genes related to G0A in lung adenocarcinoma (LUAD) was unclear. This study aimed to develop a gene signature based on for LUAD patients and investigate its relationship with prognosis, tumor immune microenvironment, and therapeutic response in LUAD. We use the TCGA-LUAD database as the discovery cohort, focusing specifically on genes associated with the G0A pathway. We used various statistical methods, including Cox and lasso regression, to develop the model. We validated the model using bulk transcriptome and single-cell transcriptome datasets (GSE50081, GSE72094, GSE127465, GSE131907 and EMTAB6149). We used GSEA enrichment and the CIBERSORT algorithm to gain insight into the annotation of the signaling pathway and the characterization of the tumor microenvironment. We evaluated the response to immunotherapy, chemotherapy, and targeted therapy in these patients. The expression of six genes was validated in cell lines by quantitative real-time PCR (qRT-PCR). Our study successfully established a six-gene signature (CHCHD4, DUT, LARP1, PTTG1IP, RBM14, and WBP11) that demonstrated significant predictive power for overall survival in patients with LUAD. It demonstrated independent prognostic value in LUAD. To enhance clinical applicability, we developed a nomogram based on this gene signature, which showed high reliability in predicting patient outcomes. Furthermore, we observed a significant association between G0A-related risk and tumor microenvironment as well as drug susceptibility, highlighting the potential of the gene signature to guide personalized treatment strategies. The expression of six genes were significantly upregulated in the LUAD cell lines. This signature holds the potential to contribute to improved prognostic prediction and new personalized therapies specifically for LUAD patients.

As the primary microtubule organizing center in animal cells, centrosome abnormalities are involved in human colon cancer.

To explore the role of centrosome-related genes (CRGs) in colon cancer.

CRGs were collected from public databases. Consensus clustering analysis was performed to separate the Cancer Genome Atlas cohort. Univariate Cox and least absolute shrinkage selection operator regression analyses were performed to identify candidate prognostic CRGs and construct a centrosome-related signature (CRS) to score colon cancer patients. A nomogram was developed to evaluate the CRS risk in colon cancer patients. An integrated bioinformatics analysis was conducted to explore the correlation between the CRS and tumor immune microenvironment and response to immunotherapy, chemotherapy, and targeted therapy. Single-cell transcriptome analysis was conducted to examine the immune cell landscape of core prognostic genes.

A total of 726 CRGs were collected from public databases. A CRS was constructed, which consisted of the following four genes: TSC1, AXIN2, COPS7A, and MTUS1. Colon cancer patients with a high-risk signature had poor survival. Patients with a high-risk signature exhibited decreased levels of plasma cells and activated memory CD4+ T cells. Regarding treatment response, patients with a high-risk signature were resistant to immunotherapy, chemotherapy, and targeted therapy. COPS7A expression was relatively high in endothelial cells and fibroblasts. MTUS1 expression was high in endothelial cells, fibroblasts, and malignant cells.

We constructed a centrosome-related prognostic signature that can accurately predict the prognosis of colon cancer patients, contributing to the development of individualized treatment for colon cancer.

Renal cell carcinoma (RCC) is known to be the most commonly diagnosed kidney cancer. Clear cell RCC (ccRCC) represents approximately 85 % of diagnosed RCC cases. Targeted therapeutics, such as multi-targeted tyrosine kinase inhibitors (TKI) and mTOR inhibitors, are widely used in ccRCC therapy. However, patients treated with mTOR and TKI inhibitors easily acquire drug resistance, making the therapy less effective. Here, we demonstrated that circPTEN inhibits the expression of its parental gene PTEN by reducing methylation of the PTEN promotor and inhibits GLUT1 expression by reducing m6A methylation of GLUT1, which suppresses ccRCC progression and resistance to mTOR inhibitors.

Previous researches have provided evidence for the significant involvement of pseudogenes in immune-related functions across different types of cancer. However, the mechanisms by which pseudogenes regulate immunity in ovarian cancer (OV) and their potential impact on clinical outcomes remain unclear. To address this gap in knowledge, our study utilized a novel computational framework to analyze a total of 491 samples from three public datasets. We employed a combination of 10 machine-learning algorithms to construct a signature known as the tumor-infiltrating immune cells-related pseudogenes signature (TIICPS). The TIICPS, consisting of 12 pseudogenes, demonstrated independent prognostic value for overall survival, surpassing conventional clinical traits, 62 published signatures, and TP53 and BRCA mutation status in three cohorts. Patients with low TIICPS exhibited heightened immune-related pathways, intricate genomic alterations, substantial immune infiltration, and greater potential for immunotherapy efficacy. Consequently, TIICPS holds promise as a predictive tool for prognosis and immunotherapy response in ovarian cancer.

Endocytosis is a complex process whereby cell surface proteins, lipids and fluid from the extracellular environment are packaged, sorted and internalized into cells. Endocytosis is also a mechanism of drug internalization into cells. There are multiple routes of endocytosis that determine the fate of molecules, from degradation in the lysosomes to recycling back to the plasma membrane. The overall rates of endocytosis and temporal regulation of molecules transiting through endocytic pathways are also intricately linked with signalling outcomes. This process relies on an array of factors, such as intrinsic amino acid motifs and post-translational modifications. Endocytosis is frequently disrupted in cancer. These disruptions lead to inappropriate retention of receptor tyrosine kinases on the tumour cell membrane, changes in the recycling of oncogenic molecules, defective signalling feedback loops and loss of cell polarity. In the past decade, endocytosis has emerged as a pivotal regulator of nutrient scavenging, response to and regulation of immune surveillance and tumour immune evasion, tumour metastasis and therapeutic drug delivery. This Review summarizes and integrates these advances into the understanding of endocytosis in cancer. The potential to regulate these pathways in the clinic to improve cancer therapy is also discussed.

Breast cancer is the most prevalent cancer, and it is accompanied by high heterogeneity. N6-methyladenosine (m6A) modification significantly contributes to breast cancer tumorigenesis and progression. However, how m6A-related genes affect the clinical outcomes and tumor immune microenvironment (TIME) of breast cancer is largely unknown. Our study developed an m6A-related gene signature on the basis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The m6A-related gene signature was constructed using univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses. Breast cancer patients were classified into low- and high-risk groups depending on the median risk score. The reliability and efficiency of the signature were validated using Kaplan-Meier analysis, receiver operating characteristic (ROC) curves, and principal component analysis (PCA). The risk score was validated as an independent indicator associated with overall survival, and a nomogram model was created to estimate the overall survival of patients with breast cancer. Functional annotation suggested that the risk score had a strong relationship with immune-related pathways. Different proportions of immune cell infiltration between the two groups were evaluated using various algorithms. The high-risk group had higher immune checkpoint expression levels. We discovered that one of the 6 prognostic genes, TMEM71, was downregulated in breast cancer tissues. In vitro experiments indicated that overexpression of TMEM71 suppressed breast cancer cell proliferation and migration. In conclusion, the m6A-related gene signature may be a sensitive biomarker for overall survival prediction and guide the individualized treatment for breast cancer patients.

Adaptin proteins (APs) play a crucial role in intracellular cell trafficking. The 'classical' role of APs is carried out by AP1‒3, which bind to clathrin, cargo, and accessory proteins. Accordingly, AP1-3 are crucial for both vesicle formation and sorting. All APs consist of four subunits that are indispensable for their functions. In fact, based on studies using cells, model organism knockdown/knock-out, and human variants, each subunit plays crucial roles and contributes to the specificity of each AP. These studies also revealed that the sorting and intracellular trafficking function of AP can exert varying effects on pathology by controlling features such as cell development, signal transduction related to the apoptosis and proliferation pathways in cancer cells, organelle integrity, receptor presentation, and viral infection. Although the roles and functions of AP1‒3 are relatively well studied, the functions of the less abundant and more recently identified APs, AP4 and AP5, are still to be investigated. Further studies on these APs may enable a better understanding and targeting of specific diseases.APs known or suggested locations and functions.