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Background: Asthma, a prevalent chronic respiratory disorder, remains enigmatic, notwithstanding considerable advancements in our comprehension. Continuous efforts are crucial for discovering novel molecular targets and gaining a comprehensive understanding of its pathogenesis. Materials and methods: In this study, we analyzed gene expression data from 212 individuals, including asthma patients and healthy controls, to identify 267 differentially expressed genes, among which C1orf64 and C7orf26 emerged as potential key genes in asthma pathogenesis. Various bioinformatics tools, including differential gene expression analysis, pathway enrichment, drug target prediction, and single-cell analysis, were employed to explore the potential roles of the genes. Results: Quantitative PCR demonstrated differential expression of C1orf64 and C7orf26 in the asthmatic airway epithelial tissue, implying their potential involvement in asthma pathogenesis. GSEA enrichment analysis revealed significant enrichment of these genes in signaling pathways associated with asthma progression, such as ABC transporters, cell cycle, CAMs, DNA replication, and the Notch signaling pathway. Drug target prediction, based on upregulated and downregulated differential expression, highlighted potential asthma treatments, including Tyrphostin-AG-126, Cephalin, Verrucarin-a, and Emetine. The selection of these drugs was based on their significance in the analysis and their established anti-inflammatory and antiviral invasion properties. Utilizing Seurat and Celldex packages for single-cell sequencing analysis unveiled disease-specific gene expression patterns and cell types. Expression of C1orf64 and C7orf26 in T cells, NK cells, and B cells, instrumental in promoting hallmark features of asthma, was observed, suggesting their potential influence on asthma development and progression. Conclusion: This study uncovers novel genetic aspects of asthma, highlighting potential therapeutic pathways. It exemplifies the power of integrative bioinformatics in decoding complex disease patterns. However, these findings require further validation, and the precise roles of C1orf64 and C7orf26 in asthma warrant additional investigation to validate their therapeutic potential. [ABSTRACT FROM AUTHOR]

Deletions of chromosome 1p36 are common in cancers; however, despite extensive studies, there has been limited success for discovering candidate tumor suppressors in this region. SRARP has recently been identified as a novel corepressor of the androgen receptor (AR) and is located on chromosome 1p36. Here, bioinformatics analysis of large tumor datasets was performed to study SRARP and its gene pair, HSPB7. In addition, using cancer cell lines, mechanisms of SRARP and HSPB7 regulation and their molecular functions were investigated. This study demonstrated that SRARP and HSPB7 are a gene pair located 5.2 kb apart on 1p36.13 and are inactivated by deletions and epigenetic silencing in malignancies. Importantly, SRARP and HSPB7 have tumor suppressor functions in clonogenicity and cell viability associated with the downregulation of Akt and ERK. SRARP expression is inversely correlated with genes that promote cell proliferation and signal transduction, which supports its functions as a tumor suppressor. In addition, AR exerts dual regulatory effects on SRARP, and although an increased AR activity suppresses SRARP transcription, a minimum level of AR activity is required to maintain baseline SRARP expression in AR+ cancer cells. Furthermore, as observed with SRARP, HSPB7 interacts with the 14‐3‐3 protein, presenting a shared molecular feature between SRARP and HSPB7. Of note, genome‐ and epigenome‐wide associations of SRARP and HSPB7 with survival strongly support their tumor suppressor functions. In particular, DNA hypermethylation, lower expression, somatic mutations, and lower copy numbers of SRARP are associated with worse cancer outcome. Moreover, DNA hypermethylation and lower expression of SRARP in normal adjacent tissues predict poor survival, suggesting that SRARP inactivation is an early event in carcinogenesis. In summary, SRARP and HSPB7 are tumor suppressors that are commonly inactivated in malignancies. SRARP inactivation is an early event in carcinogenesis that is strongly associated with worse survival, presenting potential translational applications.

Deletions of chromosome 1p36 are common in cancers; however, despite extensive studies, there has been limited success for discovering candidate tumor suppressors in this region. SRARP has recently been identified as a novel corepressor of the androgen receptor (AR) and is located on chromosome 1p36. Here, bioinformatics analysis of large tumor datasets was performed to study SRARP and its gene pair, HSPB7. In addition, using cancer cell lines, mechanisms of SRARP and HSPB7 regulation and their molecular functions were investigated. This study demonstrated that SRARP and HSPB7 are a gene pair located 5.2 kb apart on 1p36.13 and are inactivated by deletions and epigenetic silencing in malignancies. Importantly, SRARP and HSPB7 have tumor suppressor functions in clonogenicity and cell viability associated with the downregulation of Akt and ERK. SRARP expression is inversely correlated with genes that promote cell proliferation and signal transduction, which supports its functions as a tumor suppressor. In addition, AR exerts dual regulatory effects on SRARP, and although an increased AR activity suppresses SRARP transcription, a minimum level of AR activity is required to maintain baseline SRARP expression in AR+ cancer cells. Furthermore, as observed with SRARP, HSPB7 interacts with the 14‐3‐3 protein, presenting a shared molecular feature between SRARP and HSPB7. Of note, genome‐ and epigenome‐wide associations of SRARP and HSPB7 with survival strongly support their tumor suppressor functions. In particular, DNA hypermethylation, lower expression, somatic mutations, and lower copy numbers of SRARP are associated with worse cancer outcome. Moreover, DNA hypermethylation and lower expression of SRARP in normal adjacent tissues predict poor survival, suggesting that SRARP inactivation is an early event in carcinogenesis. In summary, SRARP and HSPB7 are tumor suppressors that are commonly inactivated in malignancies. SRARP inactivation is an early event in carcinogenesis that is strongly associated with worse survival, presenting potential translational applications. [ABSTRACT FROM AUTHOR]

This study investigated the network of genes that are co-expressed with androgen receptor (AR) to discover novel AR targets in breast cancer. Bioinformatics analysis of two datasets from breast cancer cell lines resulted in the identification of an AR-gene signature constituted of 98 genes that highly correlated with AR expression. Notably, C1orf64 showed the highest positive correlation with AR across the datasets with a correlation coefficient (CC) of 0.737. In addition, C1orf64 closely correlated with AR expression in primary and metastatic breast tumors and C1orf64 expression was relatively higher in breast tumors with a lower grade and lobular histology. Furthermore, there is a functional interplay between AR and C1orf64 in breast cancer. In this process, AR activation directly represses C1orf64 transcription and C1orf64, in turn, interacts with AR as a corepressor and negatively regulates the AR-mediated induction of prolactin-induced protein (PIP) and AR reporter activity. Moreover, the corepressor effect of C1orf64 results in a reduction of AR binding to PIP promoter. The other aspect of this interplay involves a cross-talk between AR and estrogen receptor (ER) signaling in which C1orf64 silencing intensifies the AR-mediated down-regulation of ER target gene, progesterone receptor. Therefore, the repression of C1orf64 by AR provides an underlying mechanism for the AR inhibitory effects on ER signaling. To elucidate the biochemical mechanisms of C1orf64 function, this study demonstrates that C1orf64 is a phosphothreonine protein that interacts with the chaperone protein 14-3-3. In summary, C1orf64 is a novel AR coregulator and a 14-3-3 binding partner in breast cancer., Competing Interests: CONFLICTS OF INTEREST The author declares no conflicts of interest.