Identification and validation of risk score model based on gene set activity as a diagnostic biomarker for endometriosis.

Objective: The enigmatic nature of Endometriosis (EMS) pathogenesis necessitates investigating alterations in signaling pathway activity to enhance our comprehension of the disease's characteristics. Methods: Three published gene expression profiles (GSE11691, GSE25628, and GSE7305 datasets) were downloaded, and the "combat" algorithm was employed for batch correction, gene expression difference analysis, and pathway enrichment difference analysis. The protein-protein interaction (PPI) network was constructed to identify core genes, and the relative enrichment degree of gene sets was evaluated. The Lasso regression model identified candidate gene sets with diagnostic value, and a risk scoring diagnostic model was constructed for further validation on the GSE86534 and GSE5108 datasets. CIBERSORT was used to assess the composition of immune cells in EMS, and the correlation between EMS diagnostic value gene sets and immune cells was evaluated. Results: A total of 568 differentially expressed genes were identified between eutopic and ectopic endometrium, with 10 core genes in the PPI network associated with cell cycle regulation. Inflammation-related pathways, including cytokine-receptor signaling and chemokine signaling pathways, were significantly more active in ectopic endometrium compared to eutopic endometrium. Diagnostic gene sets for EMS, such as homologous recombination, base excision repair, DNA replication, P53 signaling pathway, adherens junction, and SNARE interactions in vesicular transport, were identified. The risk score's area under the curve (AUC) was 0.854, as indicated by the receiver operating characteristic (ROC) curve, and the risk score's diagnostic value was validated by the validation cohort. Immune cell infiltration analysis revealed correlations between the risk score and Macrophages M2, Plasma cells, resting NK cells, activated NK cells, and regulatory T cells. Conclusion: The risk scoring diagnostic model, based on pathway activity, demonstrates high diagnostic value and offers novel insights and strategies for the clinical diagnosis and treatment of Endometriosis.

Aberrant expression of miR-153 is associated with the poor prognosis of cervical cancer.

Previous studies have demonstrated that microRNAs (miRNAs) are frequently dysregulated in tumors and are associated with the initiation and progression of various types of cancer. miR-153 has been previously shown to have an anti-tumor effect in the majority of cancer types. However, to date, the expression status and function of miR-153 in cervical cancer (CC) remains unclear. In the present study, the expression of miR-153 in CC tissues and cell lines was examined, revealing that the expression of miR-153 was markedly downregulated in the CC tissues and cell lines investigated, when compared with matched noncancerous tissues and normal cervical epithelial cell line. Furthermore, ectopic expression of miR-153 by miR-153 mimic inhibited cell proliferation; however, transfection with the miR-153 inhibitor promoted the cell proliferation in CC cell lines. Finally, the results showed that the downregulation of miR-153 was associated with poor 5-year over survival in CC patients and it could be regarded as an independent biomarker to predict the prognosis of CC patients. Collectively, these results indicated that miR-153 may function as a tumor suppressor in CC, and it may be a potential novel therapeutic target for CC.

A novel SHARPIN-PRMT5-H3R2me1 axis is essential for lung cancer cell invasion.

SHARPIN (Shank-associated RH domain interacting protein) is the main component of the linear ubiquitin chain activation complex (LUBAC). SHARPIN is involved in regulating inflammation and cancer progression. However, whether SHARPIN plays an important role in lung cancer metastasis and the potential underlying mechanism are still unknown. Here, for the first time, we reported that SHARPIN expression is closely related to lung cancer progression. Moreover, SHARPIN plays a central role in controlling lung cancer cell metastasis. Mechanistic studies further revealed that PRMT5 (Protein arginine methyltransferase 5), responsible for catalyzing arginine methylation on histones, is a novel cofactor of SHARPIN. This finding provides the basis for further study of the crosstalk between protein ubiquitination and histone methylation. We further found that SHARPIN-PRMT5 is essential for the monomethylation of histones of chromatins at key metastasis-related genes, defining a new mechanism regulating cancer invasion. A novel MLL complex (ASH2 and WDR5) was implied in the link between histone arginine2 monomethylation (H3R2me1) and histone lysine4 trimethylation (H3K4me3) for the activation of metastasis-related genes. These novel findings establish a new epigenetic paradigm in which SHARPIN-PRMT5 has distinct roles in orchestrating chromatin environments for cancer-related genes via integrating signaling between H3R2me1 and H3K4me3.