Tumor Cell-Derived Complement Component C1r Acts as a Prognostic Biomarker and Promotes Esophageal Squamous Cell Carcinoma Progression.

BACKGROUND: Mounting evidence indicates that complement components play a crucial role in cancer progression. Recent findings indicate that certain complement components display a significant rise in expression within esophageal squamous cell carcinoma (ESCC). However, the specific tumorigenic functions of these components remain unclear. This study focuses on investigating the expression pattern of C1r, elucidating a role for C1r in ESCC, as well as exploring underlying mechanisms controlled by C1r. METHODS: The expression of C1r in ESCC tissues, malignant epithelial cells, and its relationship with survival were analyzed using the Gene Expression Omnibus (GEO) database and tissue microarrays. Single-cell RNA sequencing (scRNA-seq) was used to study the expression of C1r in malignant epithelial cells. C1r knockdown or C1r overexpression in cultured ESCC cells were used to assess the effects of C1r on proliferation, migration, invasion, cell-matrix adhesion, apoptosis, and growth of xenografted tumors in immunocompromised (nude) mice. Western blotting was used to detect the expression of MMP-1 and MMP-10 in C1r knockdown or C1r overexpressing ESCC cells. RESULTS: C1r was highly expressed in ESCC tissues, malignant epithelial cells, and cultured ESCC cell lines. High C1r expression indicated a poor prognosis. Knockdown of C1r significantly suppressed the proliferation, migration, invasion, cell-matrix adhesion, and promoted apoptosis in cultured ESCC cells. Additionally, knockdown of C1r markedly inhibited tumor growth in nude mice. Overexpression of C1r had the opposite effects. C1r induced the expression of MMP-1 and MMP-10. CONCLUSIONS: C1r is highly expressed in ESCC and promotes the progression of this tumor type. Our findings suggest that C1r may serve as a novel prognostic biomarker and therapeutic target in ESCC.

MHIF-MSEA: a novel model of miRNA set enrichment analysis based on multi-source heterogeneous information fusion.

Introduction: MicroRNAs (miRNAs) are a class of non-coding RNA molecules that play a crucial role in the regulation of diverse biological processes across various organisms. Despite not encoding proteins, miRNAs have been found to have significant implications in the onset and progression of complex human diseases. Methods: Conventional methods for miRNA functional enrichment analysis have certain limitations, and we proposed a novel method called MiRNA Set Enrichment Analysis based on Multi-source Heterogeneous Information Fusion (MHIF-MSEA). Three miRNA similarity networks (miRSN-DA, miRSN-GOA, and miRSN-PPI) were constructed in MHIF-MSEA. These networks were built based on miRNA-disease association, gene ontology (GO) annotation of target genes, and protein-protein interaction of target genes, respectively. These miRNA similarity networks were fused into a single similarity network with the averaging method. This fused network served as the input for the random walk with restart algorithm, which expanded the original miRNA list. Finally, MHIF-MSEA performed enrichment analysis on the expanded list. Results and Discussion: To determine the optimal network fusion approach, three case studies were introduced: colon cancer, breast cancer, and hepatocellular carcinoma. The experimental results revealed that the miRNA-miRNA association network constructed using miRSN-DA and miRSN-GOA exhibited superior performance as the input network. Furthermore, the MHIF-MSEA model performed enrichment analysis on differentially expressed miRNAs in breast cancer and hepatocellular carcinoma. The achieved p-values were 2.17e(-75) and 1.50e(-77), and the hit rates improved by 39.01% and 44.68% compared to traditional enrichment analysis methods, respectively. These results confirm that the MHIF-MSEA method enhances the identification of enriched miRNA sets by leveraging multiple sources of heterogeneous information, leading to improved insights into the functional implications of miRNAs in complex diseases.

SAA1 regulated by S1P/S1PR1 promotes the progression of ESCC via ß-catenin activation.

Serum amyloid A1 (SAA1), an inflammation-related molecule, is associated with the malignant progression of many tumors. This study aimed to investigate the role of SAA1 in the progression of esophageal squamous cell carcinoma (ESCC) and its molecular mechanisms. The expression of SAA1 in ESCC tissues and cell lines was analyzed using bioinformatics analysis, western blotting, and reverse transcription-quantitative PCR (RT‒qPCR). SAA1-overexpressing or SAA1-knockdown ESCC cells were used to assess the effects of SAA1 on the proliferation, migration, apoptosis of cancer cells and the growth of xenograft tumors in nude mice. Western blotting, immunofluorescence and RT‒qPCR were used to investigate the relationship between SAA1 and ß-catenin and SAA1 and sphingosine 1-phosphate (S1P)/sphingosine 1-phosphate receptor 1 (S1PR1). SAA1 was highly expressed in ESCC tissues and cell lines. Overexpression of SAA1 significantly promoted the proliferation, migration and the growth of tumors in nude mice. Knockdown of SAA1 had the opposite effects and promoted the apoptosis of ESCC cells. Moreover, SAA1 overexpression promoted the phosphorylation of ß-catenin at Ser675 and increased the expression levels of the ß-catenin target genes MYC and MMP9. Knockdown of SAA1 had the opposite effects. S1P/S1PR1 upregulated SAA1 expression and ß-catenin phosphorylation at Ser675 in ESCC cells. In conclusion, SAA1 promotes the progression of ESCC by increasing ß-catenin phosphorylation at Ser675, and the S1P/S1PR1 pathway plays an important role in its upstream regulation.

Multicolor Emissive Phosphorescent Iridium(III) Complexes Containing L-Alanine Ligands: Photophysical and Electrochemical Properties, DFT Calculations, and Selective Recognition of Cu(II) Ions.

Three novel Ir(III) complexes, (ppy)2Ir(L-alanine) (Ir1) (ppy = 2-phenylpyridine), (F4ppy)2Ir(L-alanine) (Ir2) (F4ppy = 2-(4-fluorophenyl)pyridine), and (F2,4,5ppy)2Ir(L-alanine) (Ir3) (F2,4,5ppy = 2-(2,4,5-trifluorophenyl)pyridine), based on simple L-alanine as ancillary ligands were synthesized and investigated. Due to the introduction of fluorine substituents on the cyclometalated ligands, complexes Ir1-Ir3 exhibited yellow to sky-blue emissions (λem = 464-509 nm) in acetonitrile solution. The photoluminescence quantum yields (PLQYs) of Ir1-Ir3 ranged from 0.48-0.69, of which Ir3 with sky-blue luminescence had the highest PLQY of 0.69. The electrochemical study and density functional theory (DFT) calculations show that the highest occupied molecular orbital (HOMOs) energy of Ir1-Ir3 are stabilized by the introduction of fluorine substituents on the cyclometalated ligands, while L-alanine ancillary ligand has little contribution to HOMOs and lowest unoccupied molecular orbitals (LUMOs). Moreover, Ir1-Ir3 presented an excellent response to Cu2+ with a high selectivity, strong anti-interference ability, and short response time. Such a detection was based on significant phosphorescence quenching of their emissions, showing the potential application in chemosensors for Cu2+.