Human bone marrow mesenchymal stem cell-derived extracellular vesicles inhibit shoulder stiffness via let-7a/Tgfbr1 axis

Luo, Zhiwen; Sun, Yaying; Qi, Beijie; Lin, Jinrong; Chen, Yisheng; Xu, Yuzhen; Chen, Jiwu

doi:10.1016/j.bioactmat.2022.01.016

Cited by 44 publications

(51 citation statements)

References 73 publications

(93 reference statements)

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“…Functional pathway analysis included the Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO), which were analyzed by the clusterProfiler R package [ 25 , 26 ]. Gene set enrichment analysis (GSEA) was used to explore the functional pathways enriched by the dysregulated molecules.…”

Section: Methodsmentioning

confidence: 99%

Single-Cell Transcriptome Analysis Reveals the Importance of IRF1/FSTL1 in Synovial Fibroblast Subsets for the Development of Rheumatoid Arthritis

Wang

Gong

2022

Computational and Mathematical Methods in Medicine

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Objectives. This study aimed to investigate the potential role of synovial fibroblasts (SFs) in the development of rheumatoid arthritis (RA) to identify potential molecular targets and provide a theoretical basis for the treatment of RA. Methods. GSE109449, a fibroblast transcriptome dataset of synovial tissue from RA and osteoarthritis (OA), were obtained from the GEO database. After standard cell quality control, this single-cell transcriptome data was used to perform routine single-cell analysis processes. After completing dimensionality reduction, clustering, and cell subset identification of fibroblasts, the SCENIC analysis helped calculate the significant gene regulatory networks in fibroblasts and their subsets. From these computed gene regulatory networks, the regulon in which follistatin-like protein 1 (FSTL1) resides was extracted and used to analyze the transcriptional regulatory status of fibroblasts. Finally, the gene set enrichment analysis (GSEA) was used to calculate the respective enriched gene sets of IRF1 and FSTL1. Results. Three SF subgroups were identified from the single-cell transcriptome analysis; SF subset 3 was more abundant in RA than in OA ( p < 0.001 ). From the SCENIC analysis, we obtained 269 regulons and the corresponding gene regulatory networks in SF from the RA datasets. Next, we screened and obtained a regulon-containing FSTL1, where IRF1 was the major transcription factor. The top five regulons in SF subset 3 were TWIST1, MECOM, KLF6, MAFB, and RUNX1. Among the 3 SF subsets, IRF1 regulon was ranked the highest in SF subset 3. Differential analysis of pseudobulk RNA-seq showed that IRF1 was up-regulated in RA compared to OA. Between the three SF subgroups, IRF1 and FSTL1 expression was more up-regulated in SF subset 3 compared to the other two subgroups. Conclusions. IRF1 was found to regulate the invasiveness of SFs by regulating FSTL1, which may influence the disease progression of RA.

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Section: Methodsmentioning

confidence: 99%

Single-Cell Transcriptome Analysis Reveals the Importance of IRF1/FSTL1 in Synovial Fibroblast Subsets for the Development of Rheumatoid Arthritis

Wang

Gong

2022

Computational and Mathematical Methods in Medicine

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“…MicroRNAs (miRNAs) influence various physiological and pathological processes in the body through ceRNA regulatory networks [16][17][18][19][20]. Moreover, miRNAs may be released by cells and loaded into exosomes, acting as messengers for transmitting information between cells and participating in tumor development [21,22].…”

Section: Introductionmentioning

confidence: 99%

CASC1 Expression in Bladder Cancer Is Regulated by Exosomal miRNA-150: A Comprehensive Pan-Cancer and Bioinformatics Study

Luo

et al. 2022

Computational and Mathematical Methods in Medicine

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This study explored the role of cancer susceptibility 1 (CASC1) in tumorigenesis and development as well as the key pathways affecting bladder cancer progression. CASC1 was examined in various normal tissues in humans using the HPA database to quantify its expression level and subcellular localization. CASC1 is abundantly expressed in tumor tissues, primarily in cytoplasmic vesicles and stroma. TIMER2 was used to analyze the correlation between CASC1 expression levels and the types of infiltrates associated with immune cells and immunosuppressive cells. MDSC, Treg, M2, and CAF were significantly correlated with CASC1 expression in various tumors. Comparing patients with and without CASC1 mutation, those with CASC1 mutation had worse overall survival, progression-free survival, and disease-free survival. The correlation between has-miR-150 and CASC1 (for the case of bladder cancer) was then analyzed, and the related ceRNA network was mapped. A negative relationship between CASC1 expression and has-miR-150 expression was found in cases of bladder cancer. And the presence of miR-150-targeted CASC1 may be associated with bladder cancer progression. CASC1 is expressed at elevated levels in various tumor tissues, and it is associated with tumorigenesis and development. Exosomes containing miR-150-targeted CASC1 may affect the progression of bladder cancer.

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“…We conducted a qPCR on the cDNA template with TB GreenTM Premix Ex TaqTM II (Takara; RR820A) to determine the levels of mRNA. In addition, qPCR primer sets for miRNAs as well as mRNAs were obtained from RiboBio while mRNA qPCR primers have been synthesized by Sangon (Shanghai, China), as described in previous studies ( 50 ). For the relative quantification of gene expression levels, the CT method was performed in triplicates while GAPDH or U6 are included as internal controls.…”

Section: Methodsmentioning

confidence: 99%

miR-17-5p/HOXA7 Is a Potential Driver for Brain Metastasis of Lung Adenocarcinoma Related to Ferroptosis Revealed by Bioinformatic Analysis

et al. 2022

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ObjectivesPresent study aims to identify the essential mRNAs responsible for the development of brain neurovascular-related metastases (BNM) among lung adenocarcinoma (LUAD) patients. Further, we attempted to predict brain metastases more accurately and prevent their development in LUAD patients.MethodsTranscriptome data analysis was used to identify differentially expressed mRNAs (DEMs) associated with brain metastasis, and thereby the ferroptosis index (FPI) is calculated using a computational model. Meanwhile, the DEmRNAs linked with FPI, and brain metastasis were derived by the intersection of these two groups of DEMs. We also constructed a ceRNA network containing these DEmRNAs, identifying the HCP5 /hsa-miR-17-5p/HOXA7 axis for analysis. Further, a clinical cohort was employed to validate the regulatory roles of molecules involved in the ceRNA regulatory axis.ResultsHere we report the development of a ceRNA network based on BNM-associated DEMs and FPI-associated DEmRNAs which includes three core miRNAs (hsa-miR-338-3p, hsa-miR-429, and hsa-miR-17-5p), three mRNAs (HOXA7, TBX5, and TCF21), and five lncRNAs (HCP5, LINC00460, TP53TG1). Using gene set enrichment analysis (GSEA) and survival analysis, the potential axis of HCP5 /hsa-miR-17-5p/HOXA7 was further investigated. It is found that HOXA7 and ferroptosis index are positively correlated while inhibiting tumor brain metastasis. It may be that HCP5 binds competitively with miR-17-5p and upregulates HOXA7 to increase iron death limiting brain cancer metastasesConclusionsThe expression of both HOXA7 and HCP5 is positively correlated with FPI, indicating a possible link between ferroptosis and BNM. According to the results of our study, the ferroptosis-related ceRNA HCP5 /hsa-miR-17-5p/HOXA7 axis may contribute to the development of BNM in LUAD patients.

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Human bone marrow mesenchymal stem cell-derived extracellular vesicles inhibit shoulder stiffness via let-7a/Tgfbr1 axis

Cited by 44 publications

References 73 publications

Single-Cell Transcriptome Analysis Reveals the Importance of IRF1/FSTL1 in Synovial Fibroblast Subsets for the Development of Rheumatoid Arthritis

Single-Cell Transcriptome Analysis Reveals the Importance of IRF1/FSTL1 in Synovial Fibroblast Subsets for the Development of Rheumatoid Arthritis

CASC1 Expression in Bladder Cancer Is Regulated by Exosomal miRNA-150: A Comprehensive Pan-Cancer and Bioinformatics Study

miR-17-5p/HOXA7 Is a Potential Driver for Brain Metastasis of Lung Adenocarcinoma Related to Ferroptosis Revealed by Bioinformatic Analysis

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