Critical Cellular Functions and Mechanisms of Action of the RNA Helicase UAP56.

Posttranscriptional maturation and export from the nucleus to the cytoplasm are essential steps in the normal processing of many cellular RNAs. The RNA helicase UAP56 (U2AF associated protein 56; also known as DDX39B) has emerged as a critical player in facilitating and co-transcriptionally linking these steps. Originally identified as a helicase involved in pre-mRNA splicing, UAP56 has been shown to facilitate formation of the A complex during spliceosome assembly. Additionally, it has been found to be critical for interactions between components of the exon junction and transcription and export complexes to promote the loading of export receptors. Although it appears to be structurally similar to other helicase superfamily 2 members, UAP56's ability to interact with multiple different protein partners allows it to perform its various cellular functions. Herein, we describe the structure-activity relationship studies that identified protein interactions of UAP56 and its human paralog URH49 (UAP56-related helicase 49; also known as DDX39A) and are beginning to reveal molecular mechanisms by which interacting proteins and substrate RNAs may regulate these helicases. We also provide an overview of reports that have demonstrated less well-characterized roles for UAP56, including R-loop resolution and telomere maintenance. Finally, we discuss studies that indicate a potential pathogenic effect of UAP56 in the development of autoimmune diseases and cancer, and identify the association of somatic and genetic mutations in UAP56 with neurodevelopmental disorders.

Terminal regions of UAP56 and URH49 are required for their distinct complex formation functioning to an essential role in mRNA processing and export.

UAP56 and URH49 are closely related RNA helicases that function in selective mRNA processing and export pathways to fine-tune gene expression through distinct complex formations. The complex formation of UAP56 and URH49 is believed to play a crucial role in regulating target mRNAs. However, the mechanisms underlying this complex formation have not been fully elucidated. Here we identified the regions essential for the complex formation of both helicases. The terminal regions of UAP56 and the C-terminal region of URH49 were indispensable for their respective complex formation. Further analysis revealed that a specific amino acid at the C-terminus of UAP56 is critical for its complex formation. Alanine substitution of this amino acid impairs its complex formation and subsequently affected its mRNA processing and export activity. Our study provides a deeper understanding of the basis for the complex formation between UAP56 and URH49.

Structural basis for high-order complex of SARNP and DDX39B to facilitate mRNP assembly.

mRNA in eukaryotic cells is packaged into highly compacted ribonucleoprotein particles (mRNPs) in the nucleus and exported to the cytoplasm for translation. mRNP packaging and export require the evolutionarily conserved transcription-export (TREX) complex. TREX facilitates loading of various RNA-binding proteins on mRNA through the action of its DDX39B subunit. SARNP (Tho1 [transcriptional defect of Hpr1 by overexpression 1] in yeast) is shown to interact with DDX39B and affect mRNA export. The molecular mechanism of how SARNP recognizes DDX39B and functions in mRNP assembly is unclear. Here, we determine the crystal structure of a Tho1/DDX39B/RNA complex, revealing a multivalent interaction mediated by tandem DDX39B interacting motifs in SARNP/Tho1. The high-order complex of SARNP and DDX39B is evolutionarily conserved, and human SARNP can engage with five DDX39B molecules. RNA sequencing (RNA-seq) from SARNP knockdown cells shows the most affected RNAs in export are GC rich. Our work suggests the role of the high-order SARNP/DDX39B/RNA complex in mRNP assembly and export.

Nuclear mRNPs are compact particles packaged with a network of proteins promoting RNA-RNA interactions.

Messenger RNAs (mRNAs) are at the center of the central dogma of molecular biology. In eukaryotic cells, these long ribonucleic acid polymers do not exist as naked transcripts; rather, they associate with mRNA-binding proteins to form messenger ribonucleoprotein (mRNP) complexes. Recently, global proteomic and transcriptomic studies have provided comprehensive inventories of mRNP components. However, knowledge of the molecular features of distinct mRNP populations has remained elusive. We purified endogenous nuclear mRNPs from Saccharomyces cerevisiae by harnessing the mRNP biogenesis factors THO and Sub2 in biochemical procedures optimized to preserve the integrity of these transient ribonucleoprotein assemblies. We found that these mRNPs are compact particles that contain multiple copies of Yra1, an essential protein with RNA-annealing properties. To investigate their molecular and architectural organization, we used a combination of proteomics, RNA sequencing, cryo-electron microscopy, cross-linking mass spectrometry, structural models, and biochemical assays. Our findings indicate that yeast nuclear mRNPs are packaged around an intricate network of interconnected proteins capable of promoting RNA-RNA interactions via their positively charged intrinsically disordered regions. The evolutionary conservation of the major mRNA-packaging factor (yeast Yra1 and Aly/REF in metazoans) points toward a general paradigm governing nuclear mRNP packaging.

Metabolic enzyme UAP1 mediates IRF3 pyrophosphorylation to facilitate innate immune response.

Post-translational modifications (PTMs) of proteins are crucial to guarantee the proper biological functions in immune responses. Although protein phosphorylation has been extensively studied, our current knowledge of protein pyrophosphorylation, which occurs based on phosphorylation, is very limited. Protein pyrophosphorylation is originally considered to be a non-enzymatic process, and its function in immune signaling is unknown. Here, we identify a metabolic enzyme, UDP-N-acetylglucosamine pyrophosphorylase 1 (UAP1), as a pyrophosphorylase for protein serine pyrophosphorylation, by catalyzing the pyrophosphorylation of interferon regulatory factor 3 (IRF3) at serine (Ser) 386 to promote robust type I interferon (IFN) responses. Uap1 deficiency significantly impairs the activation of both DNA- and RNA-viruse-induced type I IFN pathways, and the Uap1-deficient mice are highly susceptible to lethal viral infection. Our findings demonstrate the function of protein pyrophosphorylation in the regulation of antiviral responses and provide insights into the crosstalk between metabolism and innate immunity.

Alterations in the fecal microbiota and serum metabolome in unstable angina pectoris patients.

BACKGROUND: Unstable angina pectoris (UAP) is a type of Coronary artery disease (CAD) characterized by a series of angina symptoms. Insulin-like growth factor 1 (IGF-1) system may be related to CAD. However, the correlation between the IGF-1 system, metabolism, and gut microbiota has not been studied. In the present study, we investigated the alterations of serum IGF-1 system, metabolomics, and gut microbiota in patients with UAP. METHODS: Serum and stool samples from healthy volunteers and UAP patients were collected. Serum metabolomics, PAPP-A, IGF-1, IGFBP-4, STC2, hs-CRP, TNF-α, and IL-6 were detected in serum samples by LC-MS, and commercial ELISA kits, respectively. Fecal short-chain fatty acids (SCFAs) were measured by gas chromatography. 16S rDNA was used to measure the changes of the gut microbiota. The correlation of the above indicators was analyzed. RESULTS: There were 24 upregulated and 31 downregulated metabolites in the serum of UAP patients compared to those in the controls. Pathway analysis showed that these metabolites were enriched in pathways including linoleic acid metabolism, amino acid metabolism, starch metabolism, sucrose metabolism, and citrate cycle (TCA cycle), etc. Additionally, the UAP patients had lower fecal levels of 2-hydroxyisobutyric acid and succinic acid. 16S rDNA sequencing results showed that the relative abundances of Bacteroidetes, Synergistetes, Lactobacillaceae, Burkholderiaceae, Synergistaceae, and Subdoligranulum were significantly higher in the UAP patients than the healthy subjects. Moreover, the UAP patients had lower serum IGF-1, IGFBP-4, and STC2 and higher serum inflammatory cytokines (hs-CRP, TNF-α, and IL-6) levels than the healthy controls. Furthermore, there was a strong correlation between serum amino acids and IL-6, which played an important role in the development of UAP. CONCLUSIONS: These results indicated that the UAP patients had decreased serum IGF-1 level and imbalanced amino acids metabolism, which may be caused by the altered gut microbiota. It may provide a new therapeutic strategy for unstable angina pectoris.

Identification of UAP1L1 as a critical factor for prostate cancer and underlying molecular mechanism in tumorigenicity.

BACKGROUND: Prostate cancer is the second most common cancer in men, and some new target genes are needed to predict the risk of prostate cancer progression and the treatment. METHODS: In this study, the effects of UAP1L1 (UAP1-like-1) on prostate cancer were investigated by detecting the proliferation, migration, invasion and apoptosis of prostate cancer cells in vitro using MTT, wound healing, Transwell and flow cytometry assay, and the tumor growth in vivo. The downstream genes and pathways of UAP1L1 were explored using Ingenuity Pathway Analysis (IPA), and screened by qRT-PCR and western blot. The effects of CDCA8 on prostate cancer cells were also verified in vitro, which was through detecting the change of proliferation, migration, invasion and apoptosis of prostate cancer cells after CDCA8 knockdown. RESULTS: The results indicated that UAP1L1 promoted the proliferation, migration and invasion of prostate cancer cells, which was inhibited by downregulating CDCA8. Furthermore, the promotion of CDCA8 knockdown on cell apoptosis was reduced when UAP1L1 was simultaneously overexpressed. CONCLUSIONS: In conclusion, the results in this study revealed that UAP1L1 promoted the progression of prostate cancer through the downstream gene CDCA8.

Silencing uridine diphosphate N-acetylglucosamine pyrophosphorylase gene impairs larval development in Henosepilachna vigintioctopunctata.

BACKGROUND: Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) diphosphorylase (UAP) catalyzes the formation of UDP-GlcNAc, the precursor for the production of chitin in ectodermally derived epidermal cells and midgut, for GlcNAcylation of proteins and for generation of glycosyl-phosphatidyl-inositol anchors in all tissues in Drosophila melanogaster. RESULTS: Here, we identified a putative HvUAP gene in Henosepilachna vigintioctopunctata. Knockdown of HvUAP at the second-, third- and fourth-instar stages impaired larval development. Most resultant HvUAP hypomorphs showed arrested development at the third-, fourth-instar larval or prepupal stages, and became paralyzed, depending on the age when treated. Some HvUAP-silenced larvae had weak and soft scoli. A portion of HvUAP-depleted beetles formed misshapen pupae. No HvUAP RNA interference pupae successfully emerged as adults. Dissection and microscopic observation revealed that knockdown of HvUAP affected gut growth and food ingestion, reduced cuticle thickness, and negatively affected the formation of newly generated cuticle layers during ecdysis. Furthermore, HvUAP deficiency inhibited development of the tracheal respiratory system and thinned tracheal taenidia. CONCLUSION: The phenotypical defects in HvUAP hypomorphs suggest that HvUAP is involved in the production of chitin. Moreover, our findings will enable the development of a double-stranded RNA-based pesticide to control H. vigintioctopunctata. © 2021 Society of Chemical Industry.

Medication Administration Practices in United States' Schools: A Systematic Review and Meta-synthesis.

Schools often provide medication management to children at school, yet, most U.S. schools lack a full-time, licensed nurse. Schools rely heavily on unlicensed assistive personnel (UAP) to perform such tasks. This systematic review examined medication management among K-12 school nurses. Keyword searches in three databases were performed. We included studies that examined: (a) K-12 charter, private/parochial, or public schools, (b) UAPs and licensed nurses, (c) policies and practices for medication management, or (d) nurse delegation laws. Three concepts were synthesized: (a) level of training, (b) nurse delegation, and (c) emergency medications. One-hundred twelve articles were screened. Of these, 37.5% (42/112) were comprehensively reviewed. Eighty-one percent discussed level of training, 69% nurse delegation, and 57% emergency medications. Succinct and consistent policies within and across the United States aimed at increasing access to emergency medications in schools remain necessary.

The Great Escape: mRNA Export through the Nuclear Pore Complex.

Nuclear export of messenger RNA (mRNA) through the nuclear pore complex (NPC) is an indispensable step to ensure protein translation in the cytoplasm of eukaryotic cells. mRNA is not translocated on its own, but it forms ribonuclear particles (mRNPs) in association with proteins that are crucial for its metabolism, some of which; like Mex67/MTR2-NXF1/NXT1; are key players for its translocation to the cytoplasm. In this review, I will summarize our current body of knowledge on the basic characteristics of mRNA export through the NPC. To be granted passage, the mRNP cargo needs to bind transport receptors, which facilitate the nuclear export. During NPC transport, mRNPs undergo compositional and conformational changes. The interactions between mRNP and the central channel of NPC are described; together with the multiple quality control steps that mRNPs undergo at the different rings of the NPC to ensure only proper export of mature transcripts to the cytoplasm. I conclude by mentioning new opportunities that arise from bottom up approaches for a mechanistic understanding of nuclear export.

Autologous Bone Marrow Mononuclear Cells (BMMCs) for the Treatment of Uncomplicated Grade 2 Ununited Anconeal Process (UAP) in Six Dogs: Preliminary Results.

The aim of this study was to report the results of autologous bone marrow mononuclear cell (BMMC) transplantation as a minimally invasive treatment for grade 2 UAP in dogs. This was an observational case series on six German shepherd dogs affected by grade 2 UAP as defined according to their clinical condition as well as radiographic and CT findings. Bone marrow was collected from the iliac crest and the mononuclear fraction was separated with density gradient centrifugation. Cells were suspended in fibrin glue before BMMC administration and implanted via transcutaneous injection under IB or CT guidance, using a spinal needle directly inserted into the ossification centre between the anconeal process and the olecranon. Clinical and radiographic follow-up was performed for up to 6 months. Microradiographic assessment was performed on one dog that died of other causes. A progressive reduction of pain within 3 weeks after BMMC administration was observed in all dogs, with gradually increased weight bearing on the affected limb. Radiographic and CT follow-up revealed the progressive fusion of the ossification centre at 90 days without any signs of secondary OA. The examination of microradiographs showed newly formed bone tissue in which a residue of calcified cartilage was present at the site of BMMC implantation. On the basis of these results, BMMC therapy for grade 2 UAP may be considered to be an effective and minimally invasive treatment option for dogs.

[Network Meta-analysis of clinical efficacy of Chinese herbal injection in adjuvant treatment of unstable angina pectoris].

The present study evaluated the curative efficacy of Chinese herbal injection on unstable angina pectoris( UAP) by network Meta-analysis. The databases,including Pub Med,Cochrane Library,Web of Science,CNKI,CBM,VIP and Wanfang were searched for randomized controlled trial( RCT) of Chinese herbal injection in the treatment of UAP. All researchers independently screened the articles,extracted the data and evaluated the quality. Open BUGS and Stata were employed for the analysis of the trials that met the quality standards. Fifty-eight studies were finally included in this study,involving 20 intervention measures. In terms of the effective rate,16 injections such as Dengzhan Xixin Injection,Xuesaitong Injection and Danshen Injection combined with western medicine exhibited significant efficacy. In terms of ECG,Puerarin Injection,Ginkgo Leaf Extract and Dipyridamole Injection( GDI),Breviscapine Injection combined with western medicine were superior to western medicine. In terms of the reduction of the angina attack times,Sodium Tanshinone ⅡASulfonate Injection,GDI and Dazhu Hongjingtian Injection combined with western medicine showed better effects than western medicine. In terms of shortening the angina duration,Shenmai Injection combined with western medicine was superior to western medicine. As revealed by the results,Dengzhan Xixin Injection,Xuesaitong Injection,Danshen Injection,Breviscapine Injection,Danshen Ligustrazine Injection combined with western medicine displayed prominent curative efficacy,which were recommended for clinical application. Meanwhile,appropriate intervention measures should be selected according to individual conditions. Limited by the quality of the included trials,the conclusions still need to be further verified.

Synergistic roles for human U1 snRNA stem-loops in pre-mRNA splicing.

During spliceosome assembly, interactions that bring the 5' and 3' ends of an intron in proximity are critical for the production of mature mRNA. Here, we report synergistic roles for the stem-loops 3 (SL3) and 4 (SL4) of the human U1 small nuclear RNA (snRNA) in maintaining the optimal U1 snRNP function, and formation of cross-intron contact with the U2 snRNP. We find that SL3 and SL4 bind distinct spliceosomal proteins and combining a U1 snRNA activity assay with siRNA-mediated knockdown, we demonstrate that SL3 and SL4 act through the RNA helicase UAP56 and the U2 protein SF3A1, respectively. In vitro analysis using UV crosslinking and splicing assays indicated that SL3 likely promotes the SL4-SF3A1 interaction leading to enhancement of A complex formation and pre-mRNA splicing. Overall, these results highlight the vital role of the distinct contacts of SL3 and SL4 in bridging the pre-mRNA bound U1 and U2 snRNPs during the early steps of human spliceosome assembly.

UAP1L1 plays an oncogene-like role in glioma through promoting proliferation and inhibiting apoptosis.

BACKGROUND: Uridine diphosphate-N-acetylglucosamine pyrophosphorylase-1-like-1 (UAP1L1) is involved in protein glycosylation and promotes proliferation in some tumors. By analyzing the publicly available Gene Expression Omnibus (GEO) database, we found that UAP1L1 displayed a significant change between paired glioma and normal brain tissues. The purpose of this study was to investigate the expression and functional role of UAP1L1 in glioma. METHODS: To determine the expression level of UAP1L1 in glioma, immunohistochemistry (IHC) staining was performed in tissue microarrays of 160 gliomas and 24 normal brain tissues. The correlation between UAP1L1 expression and the outcomes of glioma patients was analyzed. Human glioblastoma cell lines, U251 and U87, were employed in this study. Endogenous UAP1L1 expression in U251 and U87 cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR). A lentiviral short hairpin RNA (shRNA) vector (shUAP1L1) was constructed and used to infect U251 and U87 cells to knock down the expression of UAP1L1. We performed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, flow cytometry, human apoptosis antibody array, and in vivo subcutaneous xenograft model to investigate the biological functions of UAP1L1. RESULTS: We revealed that UAP1L1 expression was obviously upregulated in the glioma tissues. The increased UAP1L1 expression level was clinically associated with higher tumor grades and poorer patient prognoses. Moreover, we demonstrated that UAP1L1 knockdown suppressed proliferation and increased apoptosis of glioma cells in vitro. In the xenograft mouse model, we further verified that UAP1L1 knockdown could attenuate the growth of glioma cells in vivo. CONCLUSIONS: These results indicated that UAP1L1 may play an oncogene-like role in glioma, especially in high grade glioma, and thus may be of clinical importance as a future therapeutic target.

Canine Elbow Dysplasia: Ununited Anconeal Process, Osteochondritis Dissecans, and Medial Coronoid Process Disease.

Elbow dysplasia is a major cause of front limb lameness in medium to large dog breeds. Underlying causes include ununited anconeal process, medial coronoid process disease, and osteochondritis dissecans. When a definitive diagnosis of elbow dysplasia is made, the surgeon can improve elbow function but cannot entirely prevent progression of osteoarthrosis. Conventional surgical treatment with joint debridement and removal of loose osteocartilaginous bodies is not rewarding if joint incongruity persists; the result is overloading and subchondral bone exposure with erosion of the cartilage of the medial humeral condyle and medial coronoid area of the ulna leading to medial compartment disease.

Recurrent uterine artery pseudo-aneurysm requiring repeat embolization during pregnancy - A case report.

BACKGROUND: Uterine artery pseudo-aneurysms (UAP) mainly occur after traumatic delivery or traumatic pregnancy termination. A UAP can be either asymptomatic or present with symptoms such as vaginal bleeding, abdominal pain, hypovolemic shock, or fever when infected. We describe a patient diagnosed with a uterine artery pseudo-aneurysm in pregnancy that required repeat embolization. The patient had no risk factors in her recent medical history. She did, however, undergo in-vitro fertilization with oocyte retrieval performed under transvaginal ultrasonographic guidance. We suggest the hypothesis of formation of the pseudo-aneurysm secondary to vascular injury during oocyte retrieval. CASE REPORT: A 35-year-old primigravida, who conceived by in-vitro fertilization, presenting with severe abdominal pain at 19 2/7 weeks of gestation. Ultrasound examination with color doppler imaging revealed a hypo-echoic lesion with turbulent arterial flow pattern on the lower left side of the uterus. Selective catheterization and subtraction angiography permitted diagnosis of a large pseudo-aneurysm of the left uterine artery. A selective embolization was performed. Recanalization of the embolized artery was confirmed 11 weeks after initial presentation, requiring repeat embolization. A planned caesarean section was performed at 34 weeks of gestation and a healthy boy was born with a birth weight of 2065 g. CONCLUSION: Uterine artery pseudo-aneurysm is a rare but potentially life-threatening condition. It can be diagnosed using (doppler) ultrasound, revealing a hypoechoic mass with swirling blood flow. Angiography is the standard reference in diagnosing UAP and may provide definitive treatment. Management with selective unilateral uterine artery embolization appears to be safe in hemodynamically stable patients. It does not compromise uteroplacental circulation and may help to prolong the pregnancy, reducing morbidity associated with preterm birth.

Silencing of UAP1L1 inhibits proliferation and induces apoptosis in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is recognized as one of the malignant tumors with poor prognosis. UAP1L1 (UDP-N-acetylglucosamine-1-like-1) affects numerous biological processes, which is a key regulator of the development of malignant tumors. The biological function and molecular mechanism of UAP1L1 in ESCC were explored in this study. The relationship between UAP1L1 and ESCC was analyzed by immunohistochemical staining, revealing the high expression of UAP1L1 in ESCC. Importantly, the increased expression of UAP1L1 indicated the deterioration of patients' condition, which has clinical significance. Furthermore, the loss-of-function assays demonstrated that knockdown of UAP1L1 inhibited the progression of ESCC on suppressing proliferation, hindering migration, and enhancing apoptosis in vitro. Moreover, the apoptosis of ESCC cells was induced by knockdown of UAP1L1 via regulating a variety of apoptosis-related proteins, such as upregulation of Bax, CD40, CD40L, Fas, FasL, IGFBP-6, p21, p27, p53, and SMAC. Additionally, further investigation indicated that UAP1L1 by affecting the PI3K/Akt, CCND1, and MAPK promotes the progression of ESCC. In vivo xenograft model further confirmed that knockdown of UAP1L1 inhibited the development of ESCC. In conclusion, UAP1L1 was involved in the development and progression of ESCC, which may provide a powerful target for future molecular therapies.

Use of Licensed Vocational Nurses in California Schools: A Descriptive Study.

The demand for schools to provide complex health-care services for students with chronic conditions has induced districts to hire licensed vocational nurses (LVNs). Questions remain about how overlapping responsibilities and skills of nursing staff works to facilitate care. The purpose of this mixed-methods descriptive study was to examine the use of LVNs to identify factors related to the supports and impediments to school nurse (SN) practice. The sample consisted of members of the California School Nurse Organization, and methodologies consisted of an online survey and one-on-one interviews. LVNs perform duties within their scope of practice, allowing SNs time for activities related to the Framework for 21st Century School Nursing PracticeTM, confirming appropriate use, and alignment with National Association of School Nurses guidance on the utilization of LVNs. Identified areas of concern included role definition and orientation and supervision of the LVN. Insights into best practices for the effective addition of the LVN to the team are provided.

Intentions of Kentucky School Nurses to Delegate Diabetes-Related Tasks to Unlicensed Assistive Personnel.

Many children have diagnosed diabetes that must be safely managed at school. New laws have created the potential for school systems to rely more heavily on unlicensed assistive personnel (UAP) than on nurses to deliver health services, including administration of insulin injections. Using the theory of planned behavior as a framework, aims were to (1) determine the nature and extent to which health services related to diabetes were being delegated to UAP in Kentucky schools, (2) describe the attitudes of Kentucky school nurses regarding the delegation of diabetes health services to UAP, and (3) examine the relationship of selected variables to school nurses' intentions to delegate diabetes health services. Survey results revealed that school nurses in Kentucky intended to delegate some diabetes-related tasks despite their lack of support for delegation of those tasks.

Expression and Bioinformatics-Based Functional Analysis of UAP1 in Lung Adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LAD) is the most prevalent type of lung cancer. The abnormal expression of UDP-N-acetylglucosamine pyrophosphorylase 1 (UAP1) has been reported to be involved in many biological processes of cancer cells, but the expression of UAP1 in LAD is unclear. METHODS: Bioinformatics was used to analyse the LAD gene expression data and related clinical data in the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. DAVID6.8 was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) signal pathway enrichment analyses of UAP1 expression-related genes. The STRING database was used to analyse protein-protein interaction (PPI) networks. RNA isolation and reverse transcription-quantitative polymerase chain reaction (RT­qPCR) assay were used to detect the expression of UAP1 in tissues and blood samples. RESULTS: We found that UAP1 was upregulated in LAD tissues and correlated with poor clinical outcome. GO analysis showed that these genes were enriched in biological processes and functions including intracellular transport, cellular protein catabolic process, and mitochondria (P<0.05). The KEGG pathway analysis showed that these genes were mainly involved in the signalling pathways of amino sugar and nucleotide sugar metabolism, the aminoacyl-tRNA biosynthesis signalling pathway, and protein export (P<0.05). The PPI analysis showed that EPRS, COPB1, CCT3, ALDH18A1 and ARF1 genes had marked or potential interaction with UAP1 (P<0.01). In addition, UAP1 expression was upregulated in LAD tissues compared to normal tissues. High levels of UAP1 expression were associated with larger tumour sizes and later TNM stages. RT­qPCR detection in serum further showed that UAP1 expression was upregulated in the plasma of LAD patients compared to that of healthy volunteers. High expression of UAP1 in serum suggests a poor prognosis for LAD patients. CONCLUSION: UAP1 could be a novel diagnostic biomarker and a promising therapeutic target for LAD.