Single-cell analysis identifies phospholysine phosphohistidine inorganic pyrophosphate phosphatase as a target in ulcerative colitis

BACKGROUND Ulcerative colitis(UC)is a chronic gastrointestinal disorder characterized by inflammation and ulceration,representing a significant predisposition to colorectal cancer.Recent advances in single-cell RNA sequencing(scRNA-seq)technology offer a promising avenue for dissecting the complex cellular interactions and molecular signatures driving UC pathology.AIM To utilize scRNA-seq technology to dissect the complex cellular interactions and molecular signatures that underlie UC pathology.METHODS In this research,we integrated and analyzed the scRNA-seq data from UC patients.Moreover,we conducted mRNA and protein level assays as well as pathology-related staining tests on clinical patient samples.RESULTS In this study,we identified the sustained upregulation of inflammatory response pathways during UC progression,characterized the features of damaged endothelial cells in colitis.Furthermore,we uncovered the downregulation of phospholysine phosphohistidine inorganic pyrophosphate phosphatase(LHPP)has a negative correlation with signal transducer and activator of transcription 3.Significant downregulation of LHPP in UC patient tissues and plasma suggests that LHPP may serve as a potential therapeutic target for UC.This paper highlights the importance of LHPP as a potential key target in UC and unveils its potential role in inflammation regulation.CONCLUSION The findings suggest that LHPP may serve as a potential therapeutic target for UC,emphasizing its importance as a potential key target in UC and unveiling its role in inflammation regulation.

Long noncoding RNA steroid receptor RNA activator 1 inhibits proliferation and glycolysis of esophageal squamous cell carcinoma

BACKGROUND The clinical effects and detailed roles of long non-coding RNA(LncRNA)steroid receptor RNA activator 1(SRA1)in esophageal squamous cell carcinoma(ESCC)remain ambiguous.In the present study,the complementary sites between lncRNA SRA1,miRNA-363-5p,and phospholysine phosphohistidine inorganic pyrophosphate phosphatase(LHPP)predicted via bioinformatics analysis stimulated us to hypothesize that miRNA-363-5p/LHPP axis might be required for SRA1-mediated ESCC progression.AIM To investigate the molecular events of SRA1 in the malignant behavior in ESCC.METHODS Thirty-eight ESCC tissues and paired adjacent normal tissues were acquired.SRA1 expression was detected in ESCC tissues and cell lines using quantitative reverse transcription-polymerase chain reaction.Cell counting Kit-8 assay,transwell invasion assay,glycolysis assay,and xenograft tumor model were performed to address the malignant biological behaviors of ESCC cells after the introduction of SRA1.The t-test and theχ2 test were used for comparison between groups.Survival curve analysis was performed using the Kaplan-Meier method.RESULTS SRA1 downregulation was identified in ESCC.ESCC patients exhibiting a low SRA1 expression faced shorter overall survival than those with a high SRA1 expression.The introduction of SRA1 inhibited cell proliferation,glucose uptake,and lactate production in ESCC.In vivo,the growth of ESCC was hindered by SRA1 overexpression.Then,SRA1 overexpresses the LHPP by inhibiting miRNA-363-5p.Lastly,the introduction of small interfering RNA si-LHPP or miRNA-363-5p mimic could abrogate the inhibition roles triggered by SRA1.CONCLUSION SRA1 inhibits the oncogenicity of ESCC via miRNA-363-5p/LHPP axis.The SRA1/miRNA-363-5p/LHPP pathway may be a therapeutic target for ESCC.