The multiomics landscape of serum exosomes during the development of sepsis

Li, Lei; Huang, Liwei; Huang, Chenyang; Xu, Jia; Huang, Yung-Cheng; Luo, Haihua; Lu, Xinya; He, Shuyue; Yuan, Gang; Chen, Li; Han, Xue; Cao, Xusong; Jiang, Aolin; Liu, Cuiting; Shi, Jun-Min; Yang, Hong; Jiang, Yong

doi:10.1016/j.jare.2021.11.005

Cited by 18 publications

(13 citation statements)

References 71 publications

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“…These LILAR‐ regulated DEGs were visualized in a heatmap and clustered into three classes according to their expression profiles named Class I, Class II, and Class III, highlighted with larger gray font in Figure 4A. To understand the functional interactions among these gene products, we performed STRING protein–protein interaction analysis with the products of each class of genes 32 . Interestingly, there were no strong interactions in Class I and Class II genes (Figure S15).…”

Section: Resultsmentioning

confidence: 99%

LILAR, a novel long noncoding RNA regulating autophagy in the liver tissues of endotoxemic mice through a competing endogenous RNA mechanism

Tian,

Li,

Luo

et al. 2023

MedComm

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Sepsis is an often‐deadly complication of infection that can lead to multiple organ failure. Previous studies have demonstrated that autophagy has a protective effect on liver injury in sepsis. Here, we report a novel long noncoding RNA (lncRNA), named lipopolysaccharide (LPS)‐induced liver autophagy regulator (LILAR), which was highly induced in the liver tissues of endotoxemic mice. LILAR deficiency significantly increased the susceptibility of mice to LPS. In contrast, LILAR overexpression rescued the liver injury mediated by LILAR deficiency and increased the survival of LILAR knockout mice with endotoxemia. Autophagy‐related protein 13 (Atg13) is a potential downstream target gene of LILAR. LILAR deficiency notably decreased Atg13 expression and suppressed autophagy in the livers of mice challenged with LPS. A reporter gene assay showed that LILAR competitively adsorbed miR‐705 to increase the expression of Atg13 in cultured cells, indicating that LILAR participates in the regulation of the autophagy in the liver tissues of endotoxemic mice through a competitive endogenous RNA mechanism. In summary, we identified a novel lncRNA, LILAR, as a hepatic autophagy regulator, which not only promotes our understanding of liver pathophysiology but also provides a potential therapeutic target and/or diagnostic biomarker for liver injury in endotoxemia.

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Section: Resultsmentioning

confidence: 99%

LILAR, a novel long noncoding RNA regulating autophagy in the liver tissues of endotoxemic mice through a competing endogenous RNA mechanism

Tian,

Li,

Luo

et al. 2023

MedComm

Self Cite

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“…Exosomes are extracellular vesicles and are considered extracellular messengers between tumor cells and their microenvironment by exchanging and transmitting their diverse cargos, which include lncRNAs 34–38 . More significantly, exosomal lncRNAs, which demonstrate stability in blood, present themselves as potential biomarkers capable of distinguishing between individuals with tumors and healthy individuals 39–41 . In our study, exosomes from the plasma of participants with CC and healthy controls were characterized.…”

Section: Resultsmentioning

confidence: 99%

“…[34][35][36][37][38] More significantly, exosomal lncRNAs, which demonstrate stability in blood, present themselves as potential biomarkers capable of distinguishing between individuals with tumors and healthy individuals. [39][40][41] In our study, exosomes from the plasma of participants with CC and healthy controls were characterized. TEM revealed that the morphology of exosomes derived from CC was consistent with exosomes from healthy controls (Figure 8A).…”

Section: Uca1/smarcd3 Complex Contributes To Tumor Progression In Vivomentioning

confidence: 99%

lncRNA UCA1 promotes tumor progression by targeting SMARCD3 in cervical cancer

An,

Dong,

Chi

et al. 2023

Molecular Carcinogenesis

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Long noncoding RNA urothelial carcinoma associated 1 (UCA1) has been identified as a key molecule in human cancers. However, its functional implications remain unspecified in the context of cervical cancer (CC). This research aims to identify the regulatory mechanism of UCA1 in CC. UCA1 was identified through microarray and confirmed through a quantitative real‐time polymerase chain reaction. Proteins that bind with UCA1 were recognized using RNA pull‐down assays along with RNA immunoprecipitation. Ubiquitination assays and coimmunoprecipitation were performed to explore the molecular mechanisms of the SWI/SNF‐related, matrix‐associated, actin‐dependent regulator of chromatin, subfamily d, member 3 (SMARCD3) downregulated in CC. The effects of UCA1 and SMARCD3 on the progression of CC were investigated through gain‐ and loss‐of‐function assays and xenograft tumor formation in vivo. In this study, UCA1 was found to be upregulated in CC cells as well as in human plasma exosomes for the first time. Functional studies indicated that UCA1 promotes CC progression. Mechanically, UCA1 downregulated the SMARCD3 protein stabilization by promoting SMARCD3 ubiquitination. Taken together, we revealed that the UCA1/SMARCD3 axis promoted CC progression, which could provide a new therapeutic target for CC.

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“…Despite significant strides in the diagnosis and treatment of sepsis, its incidence continues to rise, underscoring the critical need for a deeper understanding of its pathogenesis. ( Li L. et al, 2022 ). More sensitive and specific targets for diagnosis and therapy must be identified through continued research efforts, as the complexities of sepsis demand a comprehensive approach to ensure effective management and prevention.…”

Section: Introductionmentioning

confidence: 99%

Identification of featured necroptosis-related genes and imbalanced immune infiltration in sepsis via machine learning

et al. 2023

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Background: The precise diagnostic and prognostic biological markers were needed in immunotherapy for sepsis. Considering the role of necroptosis and immune cell infiltration in sepsis, differentially expressed necroptosis-related genes (DE-NRGs) were identified, and the relationship between DE-NRGs and the immune microenvironment in sepsis was analyzed.Methods: Machine learning algorithms were applied for screening hub genes related to necroptosis in the training cohort. CIBERSORT algorithms were employed for immune infiltration landscape analysis. Then, the diagnostic value of these hub genes was verified by the receiver operating characteristic (ROC) curve and nomogram. In addition, consensus clustering was applied to divide the septic patients into different subgroups, and quantitative real-time PCR was used to detect the mRNA levels of the hub genes between septic patients (SP) (n = 30) and healthy controls (HC) (n = 15). Finally, a multivariate prediction model based on heart rate, temperature, white blood count and 4 hub genes was established.Results: A total of 47 DE-NRGs were identified between SP and HC and 4 hub genes (BACH2, GATA3, LEF1, and BCL2) relevant to necroptosis were screened out via multiple machine learning algorithms. The high diagnostic value of these hub genes was validated by the ROC curve and Nomogram model. Besides, the immune scores, correlation analysis and immune cell infiltrations suggested an immunosuppressive microenvironment in sepsis. Septic patients were divided into 2 clusters based on the expressions of hub genes using consensus clustering, and the immune microenvironment landscapes and immune function between the 2 clusters were significantly different. The mRNA levels of the 4 hub genes significantly decreased in SP as compared with HC. The area under the curve (AUC) was better in the multivariate prediction model than in other indicators.Conclusion: This study indicated that these necroptosis hub genes might have great potential in prognosis prediction and personalized immunotherapy for sepsis.

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The multiomics landscape of serum exosomes during the development of sepsis

Cited by 18 publications

References 71 publications

LILAR, a novel long noncoding RNA regulating autophagy in the liver tissues of endotoxemic mice through a competing endogenous RNA mechanism

LILAR, a novel long noncoding RNA regulating autophagy in the liver tissues of endotoxemic mice through a competing endogenous RNA mechanism

lncRNA UCA1 promotes tumor progression by targeting SMARCD3 in cervical cancer

Identification of featured necroptosis-related genes and imbalanced immune infiltration in sepsis via machine learning

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