Background: Alternative splicing (AS) is a molecular event that drives protein diversity through the generation of multiple mRNA isoforms. Growing evidence demonstrates that dysregulation of AS is associated with tumorigenesis. However, an integrated analysis in identifying the AS biomarkers attributed to esophageal carcinoma (ESCA) is largely unexplored. Methods: AS percent-splice-in (PSI) data were obtained from the TCGA SpliceSeq database. Univariate and multivariate Cox regression analysis was successively performed to identify the overall survival (OS)-associated AS events, followed by the construction of AS predictor through different splicing patterns. Then, a nomogram that combines the final AS predictor and clinicopathological characteristics was established. Finally, a splicing regulatory network was created according to the correlation between the AS events and the splicing factors (SF). Results: We identified a total of 2389 AS events with the potential to be used as prognostic markers that are associated with the OS of ESCA patients. Based on splicing patterns, we then built eight AS predictors that are highly capable in distinguishing highand low-risk patients, and in predicting ESCA prognosis. Notably, the area under curve (AUC) value for the exon skip (ES) prognostic predictor was shown to reach a score of 0.885, indicating that ES has the highest prediction strength in predicting ESCA prognosis. In addition, a nomogram that comprises the pathological stage and risk group was shown to be highly efficient in predicting the survival possibility of ESCA patients. Lastly, the splicing correlation network analysis revealed the opposite roles of splicing factors (SFs) in ESCA. Conclusion: In this study, the AS events may provide reliable biomarkers for the prognosis of ESCA. The splicing correlation networks could provide new insights in the identification of potential regulatory mechanisms during the ESCA development.
Breast cancer is one of the most common cancers endangering women’s health all over the world. Traditional Chinese medicine is increasingly recognized as a possible complementary and alternative therapy for breast cancer. Chaihu-Shugan-San is a traditional Chinese medicine prescription, which is extensively used in clinical practice. Its therapeutic effect on breast cancer has attracted extensive attention, but its mechanism of action is still unclear. In this study, we explored the molecular mechanism of Chaihu-Shugan-San in the treatment of breast cancer by network pharmacology. The results showed that 157 active ingredients and 8074 potential drug targets were obtained in the TCMSP database according to the screening conditions. 2384 disease targets were collected in the TTD, OMIM, DrugBank, GeneCards disease database. We applied the Bisogenet plug-in in Cytoscape 3.7.1 to obtain 451 core targets. The biological process of gene ontology (GO) involves the mRNA catabolic process, RNA catabolic process, telomere organization, nucleobase-containing compound catabolic process, heterocycle catabolic process, and so on. In cellular component, cytosolic part, focal adhesion, cell-substrate adherens junction, and cell-substrate junction are highly correlated with breast cancer. In the molecular function category, most proteins were addressed to ubiquitin-like protein ligase binding, protein domain specific binding, and Nop56p-associated pre-rRNA complex. Besides, the results of the KEGG pathway analysis showed that the pathways mainly involved in apoptosis, cell cycle, transcriptional dysregulation, endocrine resistance, and viral infection. In conclusion, the treatment of breast cancer by Chaihu-Shugan-San is the result of multicomponent, multitarget, and multipathway interaction. This study provides a certain theoretical basis for the treatment of breast cancer by Chaihu-Shugan-San and has certain reference value for the development and application of new drugs.
Hepatocellular carcinoma (HCC) is one of the most common types of malignancy and is associated with high mortality. Prior research suggests that long non-coding RNAs (lncRNAs) play a crucial role in the development of HCC. Therefore, it is necessary to identify lncRNA-associated therapeutic biomarkers to improve the accuracy of HCC prognosis. Transcriptomic data of HCC obtained from The Cancer Genome Atlas (TCGA) database were used in the present study. Differentially expressed RNAs (DERNAs), including 74 lncRNAs, 16 miRNAs, and 35 mRNAs, were identified using bioinformatics analysis. The DERNAs were subsequently used to reconstruct a competing endogenous RNA (ceRNA) network. A lncRNA signature was revealed using Cox regression analysis, including LINC00200, MIR137HG, LINC00462, AP002478.1, and HTR2A-AS1. Kaplan-Meier plot demonstrated that the lncRNA signature is highly accurate in discriminating high- and low-risk patients (P < 0.05). The area under curve (AUC) value exceeded 0.7 in both training and validation cohort, suggesting a high prognostic potential of the signature. Furthermore, multivariate Cox regression analysis indicated that both the TNM stage and the lncRNA signature could serve as independent prognostic factors for HCC (P < 0.05). Then, a nomogram comprising the TNM stage and the lncRNA signature was determined to raise the accuracy in predicting the survival of HCC patients. In the present study, we have introduced a ceRNA network that could contribute to provide a new insight into the identification of potential regulation mechanisms for the development of HCC. The five-lncRNA signature could serve as a reliable biosignature for HCC prognosis, while the nomogram possesses strong potential in clinical applications.
Bladder cancer is a common malignant tumor of the urinary system. Cystoscopy, urine cytology, and CT are the routine diagnostic methods. However, there are some problems such as low sensitivity and difficulty in staging, which must be urgently supplemented by novel diagnostic methods. Surgery, intravesical instillation, systemic chemotherapy, and radiotherapy are the main clinical treatments for bladder cancer. It is difficult for conventional treatment to deal with tumor recurrence, progression and drug resistance. In addition, the treatment agents usually have the defects of poor specific distribution ability to target tumor tissues and side effects. The rapid development of nanomedicine has brought hope for the treatment of bladder cancer in reducing side effects, enhancing tumor inhibition effects, and anti-drug resistance. Overall, we review the new progression of nano-platforms in the diagnosis and treatment of bladder cancer.
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