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Background: Hepatocellular carcinoma (HCC) is one of the most prevalent causes of cancer-related morbidity and mortality worldwide. Late-stage detection and the complex molecular mechanisms driving tumor progression contribute significantly to its poor prognosis. Dysregulated R-loops, three-stranded nucleic acid structures associated with genome instability, play a key role in the malignant characteristics of various tumors. However, the detailed role and mechanism of R-loops in HCC progression remain elusive and require further exploration. This study aimed to construct an R-loop scoring signature centered on prognosis and lipid metabolism, thereby enhancing our understanding of HCC progression and identifying potential therapeutic targets. Methods: In this study, we utilized the single-cell RNA-sequencing (scRNA-seq) data from HCC patients (GSE149614 and CRA002308) to construct an R-loop scoring model based on the identified R-loop regulator genes (RLRGs) related to HBV infection through WGCNA analysis. We also explored the tumor microenvironment and intercellular communication related to R-loop score. Additionally, a prognostic risk model based on the fatty acid metabolism-associated RLRGs was constructed using data from the TCGA database, and its association with immune infiltration, mutations, and drug sensitivity was analyzed. In vitro and in vivo experiments were performed to investigate the role of RLRG CLTC in lipid metabolism and HCC progression. Results: Using scRNA-seq data from HCC, we established an R-loop scoring model based on identified RLRGs related to HBV infection. Moreover, the more suppressive tumor immune microenvironment and stronger intercellular communication were displayed in malignant cells with high R-loop scores. The cell trajectory and cellular metabolism analysis exhibited a significant association between lipid metabolism and RLRGs. Additionally, we constructed a prognostic risk model consisting of 8 RLRGs related to fatty acid metabolism, which effectively evaluated the prognostic value, status of tumor immune microenvironment, gene mutations, and chemotherapeutic drug sensitivity for HCC patients. Notably, validation experiments suggested that CLTC could regulate lipid metabolism through R-loop formation and facilitate tumor progression in HCC. Conclusion: Collectively, our study proposes an R-loop scoring model associated with tumor immune microenvironment, lipid metabolism and prognostic value. CLTC, an R-loop regulator, emerges as a promising prognostic biomarker and therapeutic target, offering new insights into potential treatment strategies for HCC patients. [ABSTRACT FROM AUTHOR]

Background: B-cell receptor-associated protein 31 (BCAP31) is a widely expressed transmembrane protein primarily located in the endoplasmic reticulum (ER), including the ER-mitochondria associated membranes. Emerging evidence suggests that BCAP31 may play a role in cancer development and progression, although its specific effects across different cancer types remain incompletely understood. Methods: The raw data on BCAP31 expression in tumor and adjacent non-tumor (paracancerous) samples were obtained from the Broad Institute Cancer Cell Line Encyclopedia (CCLE) and UCSC databases. We also examined the association between BCAP31 expression and clinicopathological factors. Using the Cox proportional hazards model, we found that high BCAP31 levels were linked to poor prognosis. To further explore BCAP31's role, we analyzed the relationship between copy number variations (CNV) and BCAP31 mRNA expression using data from The Cancer Genome Atlas (TCGA). Additionally, the association between BCAP31 expression and signature pathway scores from the MsigDB database provided insights into the tumor biology and immunological characteristics of BCAP31.We assessed the relationship between tumor immune infiltration and BCAP31 expression using the TIMER2 and ImmuCellAI databases. The ESTIMATE computational method was employed to estimate the proportion of immune cells infiltrating the tumors, as well as the stromal and immune components, based on TCGA data. To investigate drug sensitivity in relation to BCAP31 expression, we utilized GDSC2 data, which included responses to 198 medications. We explored the relationship between BCAP31 gene expression and response to immunotherapy. Additionally, the study involved culturing KYSE-150 cells under standard conditions and using siRNA-mediated knockdown of BCAP31 to assess its function. Key experiments included Western blotting (WB) to confirm BCAP31 knockdown, MTT assays for cell proliferation, colony formation assays for growth potential, Transwell assays for migration and invasion, and wound healing assays for motility. Additionally, immunohistochemistry (IHC) was performed on tumor and adjacent normal tissue samples to evaluate BCAP31 expression levels. Results: BCAP31 was found to be significantly overexpressed in several prevalent malignancies and was associated with poor prognosis. Cox regression analysis across all cancer types revealed that higher BCAP31 levels were predominantly linked to worse overall survival (OS), disease-free interval (DFI), disease-specific survival (DSS), and progression-free interval (PFI). In most malignancies, increased BCAP31 expression was positively correlated with higher CNV. Additionally, BCAP31 expression was strongly associated with the tumor microenvironment (TME), influencing the levels of infiltrating immune cells, immune-related genes, and immune-related pathways. Drug sensitivity analysis identified six medications that showed a significant positive correlation with BCAP31 expression. Furthermore, BCAP31 expression impacted the outcomes and prognosis of cancer patients undergoing immune therapy. The functional assays demonstrated that BCAP31 knockdown in KYSE-150 cells significantly inhibited cell migration, invasion, and proliferation while enhancing colony formation ability. WB and immunohistochemistry analyses confirmed elevated BCAP31 expression in tumor tissues compared to adjacent normal tissues in esophageal cancer, lung adenocarcinoma, and gastric adenocarcinoma. Conclusion: BCAP31 has the potential to serve as a biomarker for cancer immunology, particularly in relation to immune cell infiltration, and as an indicator of poor prognosis. These findings provide a new perspective that could inform the development of more targeted cancer therapy strategies. [ABSTRACT FROM AUTHOR]

As important yield components, the genetic analysis of ear‐related traits could provide a theoretical basis for maize breeding. Here, we reported the comprehensive genetic architecture of five ear‐related traits using 150 recombinant inbred lines (RIL) populations derived from the cross between Xu178 and K12. Besides, two sets of association populations were used to dissect genetic loci of five traits by genome‐wide association study (GWAS). A total of 32 QTLs of ear‐related traits were detected in the linkage mapping. Based on the mixed linear model (MLM), a total of 117 significant SNP markers of ear‐related traits were detected. Furthermore, a combined GWAS and linkage mapping analysis revealed 51 significant SNP markers fell within the confidence interval of QTLs. A total of seven co‐located significant SNP markers among different traits were found. Finally, six important candidate genes related to grain development were screened out. In addition, through haplotype analysis, two favourable haplotypes were found on chromosome 4, which could increase row number per ear (RNE), kernel number per row (KNR) and grain yield per plant (GYP) to a certain extent. Compared with the random model, the prediction accuracy of genomic prediction (GP) was improved in different degrees by considering the significant SNP markers as fixed effects. The stable genetic QTLs, candidate genes and favourable haplotypes found in this study are valuable resources, which will provide theoretical reference for high‐yield breeding of maize. Taken together, the research results also highlight the benefits of integrating GWAS with GP to further improve the accuracy of GP. [ABSTRACT FROM AUTHOR]