ArticlePublisher preview availableLiterature Review

RNA binding motif 47 (RBM47): emerging roles in vertebrate development, RNA editing and cancer

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  • Sahlgrenska Center for Cancer Research University of Gothenburg
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Abstract and Figures

RNA-binding proteins (RBPs) are critical players in the post-transcriptional regulation of gene expression and are associated with each event in RNA metabolism. The term ‘RNA-binding motif’ (RBM) is assigned to novel RBPs with one or more RNA recognition motif (RRM) domains that are mainly involved in the nuclear processing of RNAs. RBM47 is a novel RBP conserved in vertebrates with three RRM domains whose contributions to various aspects of cellular functions are as yet emerging. Loss of RBM47 function affects head morphogenesis in zebrafish embryos and leads to perinatal lethality in mouse embryos, thereby assigning it to be an essential gene in early development of vertebrates. Its function as an essential cofactor for APOBEC1 in C to U RNA editing of several targets through substitution for A1CF in the A1CF-APOBEC1 editosome, established a new paradigm in the field. Recent advances in the understanding of its involvement in cancer progression assigned RBM47 to be a tumor suppressor that acts by inhibiting EMT and Wnt/\upbeta-catenin signaling through post-transcriptional regulation. RBM47 is also required to maintain immune homeostasis, which adds another facet to its regulatory role in cellular functions. Here, we review the emerging roles of RBM47 in various biological contexts and discuss the current gaps in our knowledge alongside future perspectives for the field.
An overview of the multifaceted functions of RBM47. It is a canonical RBP involved in post-transcriptional events such as C to U RNA editing, alternative splicing, and mRNA stabilization. a RBM47 can effectively substitute the renowned APOBEC1 cofactor A1CF, to form APOBEC1-RBM47 editosome pair that edits of several RNA targets in vitro and in vivo, establishing a new paradigm in the field [29, 45, 50]. b RBM47 is a novel post-transcriptional regulator of epithelial cell-specific alternative splicing (AS) events. In epithelial cells, it promotes the inclusion of exon 20 of TJP1 to generate a TJP1-α+ isoform. As TGF-β induced EMT significantly downregulates RBM47, exon 20 gets excluded and hence TJP1-α− isoform is expressed. Increased TJP1-α− levels impart mesenchymal characteristics [19]. c RBM47 partially exerts its tumor-suppressive function by modulating mRNA stability of DKK1 [18] and AXIN1 [66], key antagonists of Wnt/β\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\upbeta$$\end{document}-catenin signaling, and negative regulators of TGF-β-induced NRF2 pathway KEAP1 and CUL3 [63]. In immune-suppressive IL-10⁺ Bregs, RBM47 binds to 3′UTR of the Il10 mRNA and positively regulates its stability. The enhanced IL10 secretion thus reduces the severity of colitis [20]. d, e RBM47 is directly or indirectly implicated in some non-conventional functions. It positively regulates the transcription of TP53 to indirectly control P21 expression (via the p53-p21 axis) and hence has a role in influencing p53-associated cell fate decisions [70]. In zebrafish, RBM47 interacts with mitochondrial antiviral signaling protein (MAVS) and promotes its lysosome-dependent degradation through an undefined mechanism [78]. As a result, it inhibits the expression of zebrafish-specific interferons under multiple stimuli to establish immune homeostasis
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Molecular and Cellular Biochemistry (2021) 476:4493–4505
https://doi.org/10.1007/s11010-021-04256-5
RNA binding motif 47 (RBM47): emerging roles invertebrate
development, RNA editing andcancer
PavanKumarMysuruShivalingappa1· VaishaliSharma1· AnjaliShiras1· SharmilaA.Bapat1
Received: 25 May 2021 / Accepted: 31 August 2021 / Published online: 9 September 2021
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021
Abstract
RNA-binding proteins (RBPs) are critical players in the post-transcriptional regulation of gene expression and are associated
with each event in RNA metabolism. The term ‘RNA-binding motif’ (RBM) is assigned to novel RBPs with one or more
RNA recognition motif (RRM) domains that are mainly involved in the nuclear processing of RNAs. RBM47 is a novel
RBP conserved in vertebrates with three RRM domains whose contributions to various aspects of cellular functions are as
yet emerging. Loss of RBM47 function affects head morphogenesis in zebrafish embryos and leads to perinatal lethality in
mouse embryos, thereby assigning it to be an essential gene in early development of vertebrates. Its function as an essential
cofactor for APOBEC1 in C to U RNA editing of several targets through substitution for A1CF in the A1CF-APOBEC1
editosome, established a new paradigm in the field. Recent advances in the understanding of its involvement in cancer
progression assigned RBM47 to be a tumor suppressor that acts by inhibiting EMT and Wnt/
β
-catenin signaling through
post-transcriptional regulation. RBM47 is also required to maintain immune homeostasis, which adds another facet to its
regulatory role in cellular functions. Here, we review the emerging roles of RBM47 in various biological contexts and discuss
the current gaps in our knowledge alongside future perspectives for the field.
Keywords RNA-binding motif 47 (RBM47)· C to U RNA editing· Embryonic development· Cancer· EMT· Wnt/β-
catenin signaling
Introduction
Gene expression is a core cellular process regulated at mul-
tiple levels. Post-transcriptional gene regulation (PTGR), an
essential mechanism in the maintenance of cellular homeo-
stasis, controls all aspects of coding and non-coding RNAs
including co-transcriptional processing, maturation, quality
control, transport, localization, function and turn over [1].
RNA-binding proteins (RBPs) are the main players orches-
trating PTGR events through assembly with RNA molecules
in ribonucleoprotein (RNP) complexes, which are dynamic
structures that constantly change in a context-dependent
manner [2, 3]. Of the ~ 1542 RBPs encoded by the human
genome, 692 are associated with mRNP complexes that rep-
resent a highly efficient way of regulating gene expression
[3, 4]. An RBP recognizes and binds to specific sequences
and/or structural motifs in its target RNA through RNA
binding domains (RBD), prototyped by the RNA recogni-
tion motif (RRM); others include arginine-glycine-glycine
(RGG) repeats, heterogeneous ribonucleoprotein (hnRNP)
K-homology domain (KH), C3H1 zinc finger (Zf-CCCH)
domain and DEAD-box helicase domain [1, 2, 5]. The
contribution of RBPs in cell fate decisions through regula-
tion of translation, stability, and turnover of target RNAs is
well-established, further discoveries of non-coding RNAs
(microRNAs and long non-coding RNAs) in RNP complexes
revealed functional crosstalk between RBP-RNA molecules
[2]. While a set of RRM domain-containing RBPs called
RNA-Binding Motif proteins (RBM; term approved by the
HUGO gene nomenclature committee) [6] were primarily
identified to be involved in nuclear RNA processing, and are
now recognized to also perform critical roles in the regula-
tion of a wide range of cellular and physiological processes
[7, 8]. The first described RBM genes were YRRM1 and
YRRM2 (located on the Y chromosome and now designated
as RBMY), the deletions of which were implicated in male
infertility [9]. 56 human genes that include ‘RBM’ either in
* Sharmila A. Bapat
sabapat@nccs.res.in
1 National Centre forCell Science, Savitribai Phule Pune
University, Ganeshkhind, Pune411007, India
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
... Notably, our findings indicate a significant decrease in RBM47 expression in CC tissues compared with that in adjacent normal tissues. RBM47 primarily functions as an RNA-binding protein (RBP) and may potentially exert regulatory effects on DNA, thereby influencing gene regulatory functions [13]. Various cancer types can be affected by the aberrant expression of RBM47, which can affect transcriptional and post-transcriptional regulation. ...
... Verified by clinical samples, we chose RBM47 for further intensive studies. RBM47 is an RNA-binding protein that predominantly binds to introns and 3′-UTRs of its target mRNAs, thereby regulating their stability [13]. In support of our findings, RBM47 could inhibit CRC cell proliferation, invasion and migration by targeting the PTEN/PI3K/AKT signaling pathway [38]. ...
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Background Colon cancer (CC) is a malignancy associated with significant morbidity and mortality within the gastrointestinal tract. Recurrence and metastasis are the main factors affecting the prognosis of CC patients undergoing radical surgery; consequently, we attempted to determine the impact of immunity-related genes. Result We constructed a CC risk model based on ZG16, MPC1, RBM47, SMOX, CPM and DNASE1L3. Consistently, we found that a significant association was found between the expression of most characteristic genes and tumor mutation burden (TMB), microsatellite instability (MSI) and neoantigen (NEO). Additionally, a notable decrease in RBM47 expression was observed in CC tissues compared with that in normal tissues. Moreover, RBM47 expression was correlated with clinicopathological characteristics and improved disease-free survival (DFS) and overall survival (OS) among patients with CC. Lastly, immunohistochemistry and co-immunofluorescence staining revealed a clear positive correlation between RBM47 and CXCL13 in mature tertiary lymphoid structures (TLS) region. Conclusion We conclude that RBM47 was identified as a prognostic-related gene, which was of great significance to the prognosis evaluation of patients with CC and was correlated with CXCL13 in the TLS region.
... Notably, our ndings indicate a signi cant decrease in RBM47 expression in CC tissues compared with that in adjacent normal tissues. RBM47 primarily functions as an RNA-binding protein (RBP) and may potentially exert regulatory effects on DNA, thereby in uencing gene regulatory functions [13]. Various cancer types can be affected by the aberrant expression of RBM47, which can affect transcriptional and post-transcriptional regulation. ...
... Veri ed by clinical samples, we chose RBM47 for further intensive studies. RBM47 is an RNAbinding protein that predominantly binds to introns and 3′-UTRs of its target mRNAs, thereby regulating their stability [13]. In support of our ndings, RBM47 could inhibit CRC cell proliferation, invasion, and migration by targeting the PTEN/PI3K/AKT signaling pathway [38]. ...
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Full-text available
Background Colon cancer (CC) is a malignancy associated with significant morbidity and mortality within the gastrointestinal tract. Recurrence and metastasis are the main factors affecting the prognosis of CC patients undergoing radical surgery; consequently, we attempted to determine the impact of immunity-related genes. Result We constructed a CC risk model based on ZG16, MPC1, RBM47, SMOX, CPM, and DNASE1L3. Consistently, we found that a significant association was found between the expression of most characteristic genes and TMB, MSI, and NEO. Additionally, a notable decrease in RBM47 expression was observed in CC tissues compared with that in normal tissues. Moreover, RBM47 expression was correlated with clinicopathological characteristics and improved DFS and OS among patients with CC. Lastly, immunohistochemistry and co-immunofluorescence staining revealed a clear positive correlation between RBM47 and CXCL13 in mature TLS region. Conclusion We conclude that RBM47 was identified as a prognostic-related gene, which was of great significance to the prognosis evaluation of patients with CC and was correlated with CXCL13 in the TLS region.
... RBM47 is essential for embryonic endoderm development (43), and conditional expression of RBM47 alleles has been shown to cause fetal intestinal developmental defects and growth retardation (40,44). As a novel and evolutionarily conserved RNA-binding protein (RBP) in vertebrates, RBM47 is increasingly recognized for its role as a tumor regulator (45). It has been reported to be downregulated in papillary thyroid carcinoma (PTC) tissues and cells, and its overexpression can induce autophagy and suppress PTC cell proliferation (46). ...
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Background Wilms tumor (WT) is the most common pediatric kidney cancer, with survival rates exceeding 90% in localized cases. However, advanced or recurrent WT remains difficult to treat due to poor prognosis and limited knowledge of its molecular mechanisms. Gene expression profiling has shown promise in identifying prognostic markers and therapeutic targets. This study aimed to identify key prognostic genes and pathways in WT, construct risk prediction models, and validate their role in tumor progression. Methods RNA sequencing and clinical data from 136 WT patients were obtained from the TARGET database. Differential gene expression analysis was conducted using GEO datasets GSE11024 and GSE66405 to compare WT and normal kidney tissues. Identified differentially expressed genes (DEGs) underwent Gene Ontology (GO) and KEGG pathway enrichment analysis to explore biological functions and pathways associated with WT progression. Univariate Cox regression was used to assess the association between DEGs and overall survival (OS) and progression-free survival (PFS). LASSO regression models were developed for risk stratification, and model accuracy was evaluated using time-dependent ROC curves. External validation confirmed key hub genes, while functional assays in WT cell lines (WiT-49) assessed the role of GRAMD1A in tumor behavior. Results A total of 3,395 DEGs were identified, with 1,564 upregulated and 1,831 downregulated genes. Enrichment analyses revealed significant pathways involved in cell cycle regulation and metabolic reprogramming. Six key genes (GRAMD1A, PLXNA3, SPR, EBAG9, RBM47, and RIDA) were associated with both OS and PFS. LASSO models demonstrated strong predictive performance, with GRAMD1A identified as a major risk factor. External validation confirmed differential expression, and functional assays showed that GRAMD1A silencing significantly inhibited WT cell viability, proliferation, migration, and invasion. Conclusions This study identifies novel prognostic genes and potential therapeutic targets in WT. GRAMD1A, SPR, EBAG9, RBM47, and RIDA play critical roles in WT progression, with GRAMD1A as a key oncogenic factor, offering potential for risk stratification and future therapeutic intervention.
... Among these, RBM47 is a conserved RBP in vertebrates and exerts essential roles in gene regulation [6]. Functioning as a multifaceted RBP, RBM47 is involved in diverse biological and pathological processes, including early embryonic development, C to U RNA editing, and tumor suppression [7]. Decreased expression of RBM47 has been implicated in promoting proliferation and metastasis across various cancers, including breast cancer, lung adenocarcinoma, and CRC [8][9][10]. ...
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Background: Somatic copy number alterations (SCNAs) are pivotal in cancer progression and patient prognosis. Dysregulated long non-coding RNAs (lncRNAs), modulated by SCNAs, significantly impact tumorigenesis, including colorectal cancer (CRC). Nonetheless, the functional significance of lncRNAs induced by SCNAs in CRC remains largely unexplored. Methods: The dysregulated lncRNA LOC101927668, induced by copy number amplification, was identified through comprehensive bioinformatic analyses utilizing multidimensional data. Subsequent in situ hybridization was employed to ascertain the subcellular localization of LOC101927668, and gain- and loss-of-function experiments were conducted to elucidate its role in CRC progression. The downstream targets and signaling pathway influenced by LOC101927668 were identified and validated through a comprehensive approach, encompassing RNA sequencing, RT-qPCR, Western blot analysis, dual-luciferase reporter assay, evaluation of mRNA and protein degradation, and rescue experiments. Analysis of AU-rich elements (AREs) within the mRNA 3' untranslated region (UTR) of the downstream target, along with exploration of putative ARE-binding proteins, was conducted. RNA pull-down, mass spectrometry, RNA immunoprecipitation, and dual-luciferase reporter assays were employed to elucidate potential interacting proteins of LOC101927668 and further delineate the regulatory mechanism between LOC101927668 and its downstream target. Moreover, subcutaneous xenograft and orthotopic liver xenograft tumor models were utilized to evaluate the in vivo impact of LOC101927668 on CRC cells and investigate its correlation with downstream targets. Results: Significantly overexpressed LOC101927668, driven by chr7p22.3-p14.3 amplification, was markedly correlated with unfavorable clinical outcomes in our CRC patient cohort, as well as in TCGA and GEO datasets. Moreover, we demonstrated that enforced expression of LOC101927668 significantly enhanced cell proliferation, migration, and invasion, while its depletion impeded these processes in a p53-dependent manner. Mechanistically, nucleus-localized LOC101927668 recruited hnRNPD and translocated to the cytoplasm, accelerating the destabilization of RBM47 mRNA, a transcription factor of p53. As a nucleocytoplasmic shuttling protein, hnRNPD mediated RBM47 destabilization by binding to the ARE motif within RBM47 3'UTR, thereby suppressing the p53 signaling pathway and facilitating CRC progression. Conclusions: The overexpression of LOC101927668, driven by SCNAs, facilitates CRC proliferation and metastasis by recruiting hnRNPD, thus perturbing the RBM47/p53/p21 signaling pathway. These findings underscore the pivotal roles of LOC101927668 and highlight its therapeutic potential in anti-CRC interventions.
... 57 Moreover, the predicted protein structure diagram of RBM47 is most closely related to that of A1CF (45% overall identity). 58 Comprehensive analysis of clinical breast cancer gene expression databases, breast cancer progression cell line models, and mutation data from cancer genome resequencing studies revealed that RNA binding motif protein 47 (RBM47) acts as a suppressor of breast cancer progression and metastasis. RBM47 inhibits the initiation and growth of breast cancer in experimental models. ...
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Background APOBEC-1 complementation factor (A1CF) and Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-1 (APOBEC-1) constitute the minimal proteins necessary for the editing of apolipoprotein B (apoB) mRNA in vitro. Unlike APOBEC-1 and apoB mRNA, the ubiquitous expression of A1CF in human tissues suggests its unique biological significance, with various factors such as protein kinase C, thyroid hormones, and insulin regulating the activity and expression of A1CF. Nevertheless, few studies have provided an overview of this topic. Objective We conducted a literature review to describe the molecular mechanisms of A1CF and its relevance to human diseases. Method In the PubMed database, we used the keywords ‘A1CF’ and ‘APOBEC-1 complementation factor’ to collect peer-reviewed articles published in English from 2000 to 2023. Two authors independently reviewed the articles and reached the consensus. Result After reviewing 127 articles, a total of 61 articles that met the inclusion criteria were included in the present review. Studies revealed that A1CF is involved in epigenetic regulation of reproductive cells affecting embryonic development, and that it is closely associated with the occurrence of gout due to its editing properties on apoB. A1CF can also affect the process of epithelial-mesenchymal transition in renal tubular epithelial cells and promote liver regeneration by controlling the stability of IL-6 mRNA, but no influence on cardiac function was found. Furthermore, increasing evidence suggests that A1CF may promote the occurrence and development of breast cancer, lung cancer, renal cell carcinoma, hepatocellular carcinoma, endometrial cancer, and glioma. Conclusion This review clarifies the association between A1CF and other complementary factors and their impact on the development of human diseases, aiming to provide guidance for further research on A1CF, which can help treat human diseases and promote health.
... Immunofluorescence analysis indicated that the RBM47 protein was first detected in morula-stage embryos and was primarily localized in the nucleus of blastocyst embryos [89]. Previous studies by Shivalingappa et al. [90] suggested multifunctional roles of RBM47 in processes such as RNA editing and transcriptional activation during blastocyst development. In a rat experiment by Mihalik et al. [91], GPX8 was observed throughout the preimplantation period from unfertilized oocytes to blastocysts. ...
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Background Conducting genome-wide association studies (GWAS) for reproductive traits in Hanwoo cattle, including age at first calving (AFC), calving interval (CI), gestation length (GL), and number of artificial inseminations per conception (NAIPC), is of paramount significance. These analyses provided a thorough exploration of the genetic basis of these traits, facilitating the identification of key markers for targeted trait improvement. Breeders can optimize their selection strategies, leading to more efficient and sustainable breeding programs, by incorporating genetic insights. This impact extends beyond individual traits and contributes to the overall productivity and profitability of the Hanwoo beef cattle industry. Ultimately, GWAS is essential in ensuring the long-term genetic resilience and adaptability of Hanwoo cattle populations. The primary goal of this study was to identify significant single nucleotide polymorphisms (SNPs) or quantitative trait loci (QTLs) associated with the studied reproductive traits and subsequently map the underlying genes that hold promise for trait improvement. Results A genome-wide association study of reproductive traits identified 68 significant single nucleotide polymorphisms (SNPs) distributed across 29 Bos taurus autosomes (BTA). Among them, BTA14 exhibited the highest number of identified SNPs (25), whereas BTA6, BTA7, BTA8, BTA10, BTA13, BTA17, and BTA20 exhibited 8, 5, 5, 3, 8, 2, and 12 significant SNPs, respectively. Annotation of candidate genes within a 500 kb region surrounding the significant SNPs led to the identification of ten candidate genes relevant to age at first calving. These genes were: FANCG, UNC13B, TESK1, TLN1, and CREB3 on BTA8; FAM110B, UBXN2B, SDCBP, and TOX on BTA14; and MAP3K1 on BTA20. Additionally, APBA3, TCF12, and ZFR2, located on BTA7 and BTA10, were associated with the calving interval; PAX1, SGCD, and HAND1, located on BTA7 and BTA13, were linked to gestation length; and RBM47, UBE2K, and GPX8, located on BTA6 and BTA20, were linked to the number of artificial inseminations per conception in Hanwoo cows. Conclusions The findings of this study enhance our knowledge of the genetic factors that influence reproductive traits in Hanwoo cattle populations and provide a foundation for future breeding strategies focused on improving desirable traits in beef cattle. This research offers new evidence and insights into the genetic variants and genome regions associated with reproductive traits and contributes valuable information to guide future efforts in cattle breeding.
... Therefore, the precise effect and underlying mechanisms of OTUD4 for ccRCC may provide novel insights into developing combined treatments for ccRCC. RBM47 has been widely implicated in the tumorigenesis of multiple human cancers [48]. RBM47 in cancer regulates a variety of processes such as proliferation, apoptosis, autophagy, and metastasis [16,49]. ...
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Dysregulation of deubiquitination contributes to various diseases, including cancer, and aberrant expression of deubiquitinating enzymes is involved in carcinoma progression. As a member of the ovarian tumor (OTU) deubiquitinases, OTUD4 is considered a tumor suppressor in many kinds of malignancies. The biological characteristics and mechanisms of OTUD4 in clear cell renal cell carcinoma (ccRCC) remain unclear. The downregulation of OTUD4 in ccRCC was confirmed based on the TCGA database and a validation cohort of 30-paired ccRCC and para-carcinoma samples. Moreover, OTUD4 expression was detected by immunohistochemistry in 50 cases of ccRCC tissues, and patients with lower levels of OTUD4 showed larger tumor size (p = 0.015). TCGA data revealed that patients with high expression of OTUD4 had a longer overall survival rate. In vitro and in vivo studies revealed that downregulation of OTUD4 was essential for tumor cell growth and metastasis in ccRCC, and OTUD4 overexpression inhibited these malignant phenotypes. We further found that OTUD4 sensitized ccRCC cells to Erastin-induced ferroptosis, and ferrostain-1 inhibited OTUD4-induced ferroptotic cell death. Mechanistic studies indicated that OTUD4 functioned as an anti-proliferative and anti-metastasic factor through the regulation of RNA-binding protein 47 (RBM47)-mediated activating transcription factor 3 (ATF3). OTUD4 directly interacted with RBM47 and promoted its stability via deubiquitination events. RBM47 was critical in ccRCC progression by regulating ATF3 mRNA stability, thereby promoting ATF3-mediated ferroptosis. RBM47 interference abolished the suppressive role of OTUD4 overexpression in ccRCC. Our findings provide mechanistic insight into OTUD4 of ccRCC progression and indicate a novel critical pathway OTUD4/RBM47/ATF3 may serve as a potential therapeutic pathway for ccRCC.
... 26 RBM47 is an RNA-binding motif protein that plays multiple roles in bone formation and embryonic development. 27 Guan et al also pointed out that RBM47 is involved in bone formation and is associated with BMP signaling and Wnt signaling pathways. 26 Our study found a significant positive correlation between RBM47 and osteoclast differentiation function, which may suggest that RBM47 may promote osteoclast differentiation through BMP signaling, thereby affecting AS progression. ...
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Background Studies have proven that amino acid metabolism (AAM) plays an important role in ankylosing spondylitis (AS). Therefore, this study identified key AAM-related genes (AAMRGs) for the diagnosis and prediction of AS. Methods Firstly, the differentially expressed genes (DEGs) were identified between AS and normal groups in the GSE25101 and GSE73754 datasets downloaded from the Gene Expression Omnibus (GEO) database, and they were intersected to get common DEGs (Co-DEGs). Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify AS and AAM score-related genes (AS-AAMSRGs). Then, AAM related DEGs (AAMR DEGs) were acquired by intersection of Co-DEGs and AS-AAMSRGs. Moreover, the least absolute shrinkage and selection operator (LASSO) was implemented on AAMR DEGs to identify diagnostic genes, and Gene Set Enrichment Analysis (GSEA) was used to explore the functional pathways of diagnostic genes. By screening differential immune cells, the correlation between differential immune cells and diagnostic genes was further analyzed. Finally, miRNA-mRNA networks were constructed and drug prediction analysis was performed. Results By overlapping to obtain three AAMR DEGs (TP53INP1, TUBB and RBM47). The results of nomogram and decision curve analysis (DCA) suggested that three AAMR DEGs had diagnostic value for AS and significantly enriched to neutrophil activation, neutrophil degranulation. The proportion of eight kinds of immune cells in AS and normal groups was significantly different, such as activated dendritic cell, CD56 bright natural killer cell, effector memory CD4 T cell. In the miRNA-mRNA regulatory networks, three miRNAs (has-miR-429, has-miR-200c-3p, has-miR-200b-3p) could regulate TP53INP1 and TUBB. There was only one miRNA (has-miR-122-5p) could regulate RBM47. Finally, 51 target drugs (such as colchicine, vinblastine, vincristine) were associated with TUBB. Conclusion TP53INP1, TUBB and RBM47 might play key roles in AS and could be used as potential biomarkers of AS.
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