AP-64, Encoded by C5orf46, Exhibits Antimicrobial Activity against Gram-Negative Bacteria

Zhong, Kunhong; Wang, Yuelong; Wang, Zeng; Zhang, Zongliang; Zhao, Shasha; Li, Hexian; Huang, Jianhan; Guo, Wenhao; Zheng, Xi; Guo, Gang; Zhou, Liangxue; Yang, Huijuan; Tong, Aiping

doi:10.3390/biom11040485

Cited by 8 publications

(4 citation statements)

References 20 publications

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“…In total, micro-proteins with Mw from five to 20 kDa are almost 38%. It is known that micro-proteins possess a number of beneficial biological activities, for example, C5orf46 protein possesses antimicrobial activity [ 27 ]. It is also interesting that the micro-protein C19orf48 is widely expressed in cancers and can be processed for cytotoxic T lymphocyte (CTL) recognition [ 28 ].…”

Section: Resultsmentioning

confidence: 99%

Uncharacterized Proteins CxORFx: Subinteractome Analysis and Prognostic Significance in Cancers

Ершов

Yablokov

Mezentsev

et al. 2023

IJMS

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Functions of about 10% of all the proteins and their associations with diseases are poorly annotated or not annotated at all. Among these proteins, there is a group of uncharacterized chromosome-specific open-reading frame genes (CxORFx) from the ‘Tdark’ category. The aim of the work was to reveal associations of CxORFx gene expression and ORF proteins’ subinteractomes with cancer-driven cellular processes and molecular pathways. We performed systems biology and bioinformatic analysis of 219 differentially expressed CxORFx genes in cancers, an estimation of prognostic significance of novel transcriptomic signatures and analysis of subinteractome composition using several web servers (GEPIA2, KMplotter, ROC-plotter, TIMER, cBioPortal, DepMap, EnrichR, PepPSy, cProSite, WebGestalt, CancerGeneNet, PathwAX II and FunCoup). The subinteractome of each ORF protein was revealed using ten different data sources on physical protein–protein interactions (PPIs) to obtain representative datasets for the exploration of possible cellular functions of ORF proteins through a spectrum of neighboring annotated protein partners. A total of 42 out of 219 presumably cancer-associated ORF proteins and 30 cancer-dependent binary PPIs were found. Additionally, a bibliometric analysis of 204 publications allowed us to retrieve biomedical terms related to ORF genes. In spite of recent progress in functional studies of ORF genes, the current investigations aim at finding out the prognostic value of CxORFx expression patterns in cancers. The results obtained expand the understanding of the possible functions of the poorly annotated CxORFx in the cancer context.

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Section: Resultsmentioning

confidence: 99%

Uncharacterized Proteins CxORFx: Subinteractome Analysis and Prognostic Significance in Cancers

Ершов

Yablokov

Mezentsev

et al. 2023

IJMS

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“…FAM71F1 has mostly been studied in spermatogenesis as it controls acrosome assembly and male fertility [27] which is a phenotype in CFTR deficient patients and whether there is a direct link of CFTR and FAM71F1 in these tissues remains to be determined. C5orf46 is expressed in epithelial cells and has recently been reported to encode an antimicrobial protein with activity against gram negative bacteria [28] . Overall, these data provided a comprehensive resource for the CF community and support the existence of immunological changes in the CF airway independent of infections.…”

Section: Discussionmentioning

confidence: 99%

Multi-omic comparisons between CFBE41o- cells stably expressing wild-type CFTR and F508del-mutant CFTR

Kolls

2023

Journal of Cystic Fibrosis

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“…RNA-seq results revealed that C5ORF46 is the most downregulated gene in lesioned VHE skin (Voorberg et al, 2021). Further, C5ORF46 has Frontiers in Genetics frontiersin.org been shown to encode an antimicrobial peptide AP-64, and exhibit antimicrobial activity against gram-negative bacteria (Zhong et al, 2021). C5ORF46 is thought to interact with TMBIM6, a protein that regulates calcium homeostasis in the endoplasmic reticulum (Voorberg et al, 2021;BioGRID, 2022).…”

Section: Discussionmentioning

confidence: 99%

A systematic analysis of C5ORF46 in gastrointestinal tumors as a potential prognostic and immunological biomarker

Jiang

Wang²,

Li³

et al. 2022

Front. Genet.

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Background: Chromosome 5 open reading frame 46 (C5ORF46), also known as antimicrobial peptide with 64 amino acid residues (AP-64) and skin and saliva-secreted protein 1 (SSSP1), belongs to the family of open reading frame genes and encodes a small exosomal protein. C5ORF46 has been implicated in antibacterial activity and associated with patient prognosis in pancreatic cancer, colorectal cancer, and stomach cancer. These findings highlight the importance of C5ORF46 in gastrointestinal (GI) tumor inception and development. However, the prognostic and immunological value of C5ORF46 in human GI tumors remains largely unknown. In this study, we sought to explore the potential value of C5ORF46 in GI tumor prognosis and immunology.Method: RNA sequencing (RNA-seq) was performed on the tumor and tumor-adjacent normal samples we collected to identify potential target genes for GI tumors. Apart from our RNA-seq data, all original data were downloaded from The Cancer Genome Atlas (TCGA) database and integrated via Strawberry Perl (v 5.32.0) and R (v 4.1.1). The differential expression of C5ORF46 was examined with Oncomine, Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), Cancer Cell Line Encyclopedia (CCLE), the Human Protein Atlas (HPA) and TCGA databases. The c-BioPortal database was used to investigate the genomic alterations of C5ORF46. The effect of C5ORF46 on prognosis and clinical phenotypes was explored via bioinformatics analyses on the TCGA and GEPIA databases. We used the bioinformatics analyses based on the TCGA database to analyze tumor mutational burden (TMB), microsatellite instability (MSI), tumor immune cell infiltration, and the correlations between C5ORF46 expression and several immune-related genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was carried out via the DAVID website and presented as bubble charts using ShengXinRen online tools. Gene set enrichment analysis (GSEA) was performed using R scripts based on data downloaded from the GSEA website. Immunohistochemistry (IHC) was used to validate the expression of C5ORF46 in GI tumors.Results: The results of our RNA-seq data indicated a critical role for C5ORF46 in colon carcinogenesis. Consistently, we demonstrated that C5ORF46 was highly expressed in tumor tissues compared to normal tissues in human GI tumors. Moreover, a strong correlation was observed between C5ORF46 expression levels and patient prognosis, staging, TMB, MSI, and immune cell infiltration. Further, C5ORF46 presented as an important regulator in the tumor microenvironment (TME) and was active in the regulation of cancer immune functions. C5ORF46 is significantly correlated with genes regulating inflammation and immune responses.Conclusion:C5ORF46 may serve as a biomarker for GI tumor prognosis and immunology. C5ORF46 could be a novel target for GI tumor immunotherapy.

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AP-64, Encoded by C5orf46, Exhibits Antimicrobial Activity against Gram-Negative Bacteria

Cited by 8 publications

References 20 publications

Uncharacterized Proteins CxORFx: Subinteractome Analysis and Prognostic Significance in Cancers

Uncharacterized Proteins CxORFx: Subinteractome Analysis and Prognostic Significance in Cancers

Multi-omic comparisons between CFBE41o- cells stably expressing wild-type CFTR and F508del-mutant CFTR

A systematic analysis of C5ORF46 in gastrointestinal tumors as a potential prognostic and immunological biomarker

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