The systematic identification of survival-related alternative splicing events and splicing factors in glioblastoma.

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor, making it one of the most life-threatening human cancers. Nevertheless, research on the mechanism of action between alternative splicing (AS) and splicing factor (SF) or biomarkers in GBM is limited. AS is a crucial post-transcriptional regulatory mechanism. More than 95% of human genes undergo AS events. AS can diversify the expression patterns of genes, thereby increasing the diversity of proteins and playing a significant role in the occurrence and development of tumors. In this study, we downloaded 599 clinical data and 169 transcriptome analysis data from The Cancer Genome Atlas (TCGA) database. Besides, we collected AS data about GBM from TCGA-SpliceSeq. The overall survival (OS) related AS events in GBM were determined through least absolute shrinkage and selection operator (Lasso) and Cox analysis. Subsequently, the association of these 1825 OS-related AS events with patient survival was validated using the Kaplan-Meier survival analysis, receiver operating characteristic curve, risk curve analysis, and independent prognostic analysis. Finally, we depicted the AS-SF regulatory network, illustrating the interactions between splicing factors and various AS events in GBM. Additionally, we identified three splicing factors (RNU4-1, SEC31B, and CLK1) associated with patient survival. In conclusion, based on AS occurrences, we developed a predictive risk model and constructed an interaction network between GBM-related AS events and SFs, aiming to shed light on the underlying mechanisms of GBM pathogenesis and progression.

Pharmacological activity of capsaicin: Mechanisms and controversies (Review).

Capsaicin, which is abundant in chili peppers, exerts antioxidative, antitumor, antiulcer and analgesic effects and it has demonstrated potential as a treatment for cardiovascular, gastrointestinal, oncological and dermatological conditions. Unique among natural irritants, capsaicin initially excites neurons but then 'calms' them into long­lasting non­responsiveness. Capsaicin can also promote weight loss, making it potentially useful for treating obesity. Several mechanisms have been proposed to explain the therapeutic effects of capsaicin, including antioxidation, analgesia and promotion of apoptosis. Some of the mechanisms are proposed to be mediated by the capsaicin receptor (transient receptor potential cation channel subfamily V member 1), but some are proposed to be independent of that receptor. The clinical usefulness of capsaicin is limited by its short half­life. The present review provided an overview of what is known about the therapeutic effects of capsaicin and the mechanisms involved and certain studies arguing against its clinical use were mentioned.

Mechanisms of action of triptolide against colorectal cancer: insights from proteomic and phosphoproteomic analyses.

Triptolide is a potent anti-inflammatory agent that also possesses anticancer activity, including against colorectal cancer (CRC), one of the most frequent cancers around the world. In order to clarify how triptolide may be effective against CRC, we analyzed the proteome and phosphoproteome of CRC cell line HCT116 after incubation for 48 h with the drug (40 nM) or vehicle. Tandem mass tagging led to the identification of 403 proteins whose levels increased and 559 whose levels decreased in the presence of triptolide. We also identified 3,110 sites in proteins that were phosphorylated at higher levels and 3,161 sites phosphorylated at lower levels in the presence of the drug. Analysis of these differentially expressed and/or phosphorylated proteins showed that they were enriched in pathways involving ribosome biogenesis, PI3K-Akt signaling, MAPK signaling, nucleic acid binding as well as other pathways. Protein-protein interactions were explored using the STRING database, and we identified nine protein modules and 15 hub proteins. Finally, we identified 57 motifs using motif analysis of phosphosites and found 16 motifs were experimentally verified for known protein kinases, while 41 appear to be novel. These findings may help clarify how triptolide works against CRC and may guide the development of novel treatments.

Network models of prostate cancer immune microenvironments identify ROMO1 as heterogeneity and prognostic marker.

Prostate cancer (PCa) is the fifth leading cause of death from cancer in men worldwide. Its treatment remains challenging due to the heterogeneity of the tumor, mainly because of the lack of effective and targeted prognostic markers at the system biology level. First, the data were retrieved from TCGA dataset, and valid samples were obtained by consistent clustering and principal component analysis; next, key genes were analyzed for prognosis of PCa using WGCNA, MEGENA, and LASSO Cox regression model analysis, while key genes were screened based on disease-free survival significance. Finally, TIMER data were selected to explore the relationship between genes and tumor immune infiltration, and GSCAlite was used to explore the small-molecule targeted drugs that act with them. Here, we used tumor subtype analysis and an energetic co-expression network algorithm of WGCNA and MEGENA to identify a signal dominated by the ROMO1 to predict PCa prognosis. Cox regression analysis of ROMO1 was an independent influence, and the prognostic value of this biomarker was validated in the training set, the validated data itself, and external data, respectively. This biomarker correlates with tumor immune infiltration and has a high degree of infiltration, poor prognosis, and strong correlation with CD8+T cells. Gene function annotation and other analyses also implied a potential molecular mechanism for ROMO1. In conclusion, we putative ROMO1 as a portal key prognostic gene for the diagnosis and prognosis of PCa, which provides new insights into the diagnosis and treatment of PCa.