Prostate cancer (PCa) is the third most common reason of cancer-related deaths in men. Accumulating evidence has shown that dysregulation of long noncoding RNAs (lncRNAs) is closely related to cancer initiation and development. Although large numbers of lncRNAs have been discovered, knowledge regarding their function and physiological/pathological significance remains limited. In this study, we aimed to reveal functional lncRNAs and identify prognosis-related RNAs in PCa by analyzing data from The Cancer Genome Atlas (TCGA). To achieve this, an lncRNA-mRNA coexpression network was constructed by weighted correlation network analysis. Additionally, a subnetwork was extracted from this weighted correlation network, and seven lncRNAs were identified as core nodes. Further Kaplan-Meier survival analysis showed that three lncRNAs (LINC00683, LINC00857, and FENDRR) were significantly downregulated in PCa samples, and there was a strong positive correlation with patient survival. Importantly, LINC00683 has not been fully reported as related with PCa. Additionally, gene set enrichment analysis indicated that LINC00683 might be involved in cancer-related pathways such as the Wnt pathway. Based on the findings of this study, lncRNA LINC00683 is likely to provide a new diagnostic biomarker and therapeutic target for future PCa treatments.

Coronary artery disease (CAD) is considered one of the leading causes of death worldwide. Although dysregulation of long non-coding RNAs (lncRNAs) has been reported to be associated with the initiation and progression of CAD, the knowledge regarding their specific functions as well their physiological/pathological significance in CAD is very limited. In this study, we aimed to systematically analyze immune-related lncRNAs in CAD and explore the relationship between key immune-related lncRNAs and the immune cell infiltration process. Based on differential expression analysis of mRNAs and lncRNAs, an immune-related lncRNA-mRNA weighted gene co-expression network containing 377 lncRNAs and 119 mRNAs was constructed. LINC01480 and AL359237.1 were identified as the hub immune-related lncRNAs in CAD using the random forest-recursive feature elimination and least absolute shrinkage and selection operator logistic regression. Furthermore, 93 CAD samples were divided into two subgroups according to the expression values of LINC01480 and AL359237.1 by consensus clustering analysis. By performing gene set enrichment analysis, we found that cluster 2 enriched more cardiovascular risk pathways than cluster 1. The immune cell infiltration analysis of ischemic cardiomyopathy (ICM; an advanced stage of CAD) samples revealed that the proportion of macrophage M2 was upregulated in the LINC01480 highly expressed samples, thus suggesting that LINC01480 plays a protective role in the progression of ICM. Based on the findings of this study, lncRNA LINC01480 may be used as a novel biomarker and therapeutic target for CAD.

Bruton's tyrosine kinase (BTK) plays a vital role in mature B-cell proliferation, development and function. Its inhibitors have gradually been applied for the treatment of many B-cell malignancies. However, because of treatment-associated drug resistance or low efficacy, it is urgent to develop new inhibitors and/or improve the efficacy of current inhibitors, where finding the intrinsic activation mechanism becomes the key to solve this problem. Here, we used BTK T474M mutation as a resistance model for inhibitors to study the mechanism of BTK activation and drug resistance by free molecular dynamics simulations. The results showed that the increase of kinase activity of T474M mutation is coming from the conformation change of the activation ring and ATP binding sites located in BTK N-terminus region. Specifically, the Thr 474 mutation changed the structure of A-loop and stabilized the binding site of ATP, thus promoting the catalytic ability in the kinase domain. This localized dynamics-driven activation mechanism and resistance mechanism of BTK may provide new ideas for drug development in B-cell malignancies.