Long Noncoding RNA: Regulatory Mechanisms and Therapeutic Potential in Sepsis

Wang, Wei; Yang, Ni; Wen, Ri; Liu, Chunfeng; Zhang, Tie-Ning

doi:10.3389/fcimb.2021.563126

Cited by 32 publications

(29 citation statements)

References 122 publications

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“…Accumulating evidence reveals the significant roles of lncRNAs in sepsis‐induced cardiac dysfunction 17,18 . One of the best‐studied lncRNA is MALAT1.…”

Section: Discussionmentioning

confidence: 99%

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LncRNA small nucleolar RNA host gene 16 reduces sepsis‐induced myocardial damage by regulating miR‐421/suppressor of cytokine signaling 5 axis

Xie

et al. 2022

The Kaohsiung J of Med Scie

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Currently, sepsis‐induced cardiomyopathy (SIC) remains as one of the most critical clinical syndromes in terminally ill patients. Noncoding RNAs (including microRNAs and long noncoding RNAs) are implicated in both the onset and development of SIC. We herein investigated the functional role and molecular target of long noncoding RNA small nucleolar RNA host gene 16 (SNHG16) in an in vitro SIC model of H9c2 myocardial cells. We used lipopolysaccharide (LPS) as endotoxin to treat H9c2 cells to mimic SIC damages. Cell Counting Kit 8 and apoptosis assay were performed to assess cell proliferation and cell death. Quantitative real‐time‐PCR and Western blot were employed to examine gene expression level at mRNA and protein level. Dual luciferase assay is used to validate the functional interactions between SNHG16/mi‐R421 and miR‐421/suppressor of cytokine signaling 5 (SOCS5). Inflammatory cytokines were measured by ELISA. Superoxide dismutase and malondialdehyde measurement was performed to assess oxidative stress, which was further confirmed by 2′,7′‐dichlorofluorescin diacetate staining. Our data demonstrated that in the LPS‐induced sepsis model of myocardial cells, SNHG16 overexpression downregulated the expression level of miR‐421, which sustained the expression of SOCS5 to alleviate the adverse effects of LPS, such as apoptosis, pro‐inflammatory cytokines, and oxidative stress. Our data suggest that SNHG16 functions as a ceRNA to maintain SOCS5 level by targeting miR‐421, thereby attenuating LPS‐induced myocardial cell damages. Targeting miR‐421 or modulating lncRNA SNHG16 level may be leveraged as a beneficial strategy against sepsis‐induced cellular damage in cardiomyocytes.

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“…Accumulating evidence reveals the significant roles of lncRNAs in sepsis‐induced cardiac dysfunction 17,18 . One of the best‐studied lncRNA is MALAT1.…”

Section: Discussionmentioning

confidence: 99%

“…Accumulating evidence reveals the significant roles of lncRNAs in sepsis-induced cardiac dysfunction. 17,18 One of the best-studied lncRNA is MALAT1. Another study showed that MALAT1 depletion could decrease the inflammatory response in H9c2 cells.…”

Section: Discussionmentioning

confidence: 99%

LncRNA small nucleolar RNA host gene 16 reduces sepsis‐induced myocardial damage by regulating miR‐421/suppressor of cytokine signaling 5 axis

Xie

et al. 2022

The Kaohsiung J of Med Scie

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“…Although lacking of protein-coding capacity, lncRNA has been found to be related to so many pathological processes of human diseases, such as cancer and inflammatory response ( 4 , 6 ). Recently, emerging studies have revealed that some lncRNAs, such as NEAT1, MALAT1, and ANRIL, could participate in the progression of sepsis and serve as a potential biomarker for sepsis ( 7 – 9 ). LincRNA-NR_024015 , also known as Testis development related gene 1 ( TDRG1 ), is a newly identified tumor-associated lncRNA.…”

Section: Introductionmentioning

confidence: 99%

The rs8506 TT Genotype in lincRNA-NR_024015 Contributes to the Risk of Sepsis in a Southern Chinese Child Population

Zhou²,

Wei³

et al. 2022

Front. Public Health

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BackgroundSepsis is a highly life-threatening heterogeneous syndrome and a global health burden. Studies have shown that many genetic variants could influence the risk of sepsis. Long non-coding RNA lincRNA-NR_024015 may participate in functional alteration of endothelial cell via vascular endothelial growth factor (VEGF) signaling, whereas its relevance between the lincRNA-NR_024015 polymorphism and sepsis susceptibility is still unclear.Methods474 sepsis patients and 678 healthy controls were enrolled from a southern Chinese child population in the present study. The polymorphism of rs8506 in lincRNA-NR_024015 was determined using Taqman methodology.ResultsOverall, a significant association was found between rs8506 polymorphism and the risk of sepsis disease (TT vs. CC/CT: adjusted OR = 1.751, 95%CI = 1.024–2.993, P = 0.0406). In the stratified analysis, the results suggested that the carriers of TT genotypes had a significantly increased sepsis risk among the children aged 12–60 months, females, early-stage sepsis and survivors (TT vs. CC/CT: ORage = 2.413; ORfemale = 2.868; ORsepsis = 2.533; ORsurvivor = 1.822; adjusted for age and gender, P < 0.05, respectively).ConclusionOur study indicated that lincRNA-NR_024015 rs8506 TT genotype might contribute to the risk of sepsis in a southern Chinese child population. Future research is required to elucidate the possible immunoregulatory mechanisms of this association and advance the development of novel biomarkers in sepsis.

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“…14,15 Although dysregulated expression of the lncRNAs mentioned above was associated with sepsis etiopathology in adults, no studies have explored their potential clinical utility as diagnostic and/or prognostic biomarkers in neonatal sepsis. 16 To this end, the authors were inspired to explore the potential clinical utility of the lncRNAs MALAT1, ANRIL, and HOTAIR in a sample of neonatal sepsis to confirm their rules in this devastating disorder. The results of this work could help in risk stratification for this vulnerable group of population and provide preliminary data for future molecular targeted therapy.…”

Section: Introductionmentioning

confidence: 99%

Long Non-Coding RNAs ANRIL and HOTAIR Upregulation is Associated with Survival in Neonates with Sepsis in a Neonatal Intensive Care Unit

AbdAllah¹,

Ageeli²,

Shbeer³

et al. 2022

IJGM

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Background Recently, long non-coding RNAs (lncRNAs) have emerged as potential molecular biomarkers for sepsis. We aimed to profile the expression signature of three inflammation-related lncRNAs, MALAT1, ANRIL, and HHOTAIR, in the plasma of neonates with sepsis and correlate these signatures with the phenotype. Patients and Methods This case–control study included 124 neonates with sepsis (88 survivors/36 non-survivors) admitted to the neonatal ICU and 17 healthy neonates. The relative expressions were quantified by real-time PCR and correlated to the clinic-laboratory data. Results The three circulating lncRNAs were upregulated in the cases; the median levels were MALAT1 (median = 1.71, IQR: −0.5 to 3.27), ANRIL (median = 1.09, IQR: 0.89 to 1.30), and HOTAIR (median = 1.83, IQR: 1.44 to 2.41). Co-expression analysis showed that the three studied lncRNAs were directly correlated (all p -values <0.001). Overall and stratification by sex analyses revealed significantly higher levels of the three lncRNAs in non-survivors compared to the survivor group (all p -values <0.001). Principal component analysis showed a clear demarcation between the two study cohorts in males and females. Cohorts with upregulated ANRIL (hazard ratio; HR = 4.21, 95% CI = 1.15–10.4, p =0.030) and HOTAIR (HR = 2.49, 95% CI = 1.02–6.05, p =0.044) were at a higher risk of mortality. Conclusion Circulatory MALAT1, ANRIL, and HOTAIR were upregulated in neonatal sepsis, and the latter two may have the potential as prognostic biomarkers for survival in neonatal sepsis.

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Long Noncoding RNA: Regulatory Mechanisms and Therapeutic Potential in Sepsis

Cited by 32 publications

References 122 publications

LncRNA small nucleolar RNA host gene 16 reduces sepsis‐induced myocardial damage by regulating miR‐421/suppressor of cytokine signaling 5 axis

LncRNA small nucleolar RNA host gene 16 reduces sepsis‐induced myocardial damage by regulating miR‐421/suppressor of cytokine signaling 5 axis

The rs8506 TT Genotype in lincRNA-NR_024015 Contributes to the Risk of Sepsis in a Southern Chinese Child Population

Long Non-Coding RNAs ANRIL and HOTAIR Upregulation is Associated with Survival in Neonates with Sepsis in a Neonatal Intensive Care Unit

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