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http://purl.uniprot.org/citations/34484222http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/34484222http://www.w3.org/2000/01/rdf-schema#comment"

Background

Unexplained recurrent spontaneous abortion (URSA) is a common pregnancy complication and the etiology is unknown. URSA-associated lncRNAs are expected to be potential biomarkers for diagnosis, and might be related to the disease pathogenesis.

Objective

To investigate differential lncRNAs in peripheral blood of non-pregnant URSA patients and matched healthy control women and to explore the possible mechanism of differential lncRNAs leading to URSA.

Methods

We profiled lncRNAs expression in peripheral blood from 5 non-pregnant URSA patients and 5 matched healthy control women by lncRNA microarray analysis. Functions of URSA-associated lncRNAs were further investigated in vitro.

Results

RP11-115N4.1 was identified as the most differentially expressed lncRNA which was highly upregulated in peripheral blood of non-pregnant URSA patients (P = 3.63E-07, Fold change = 2.96), and this dysregulation was further validated in approximately 26.67% additional patients (4/15). RP11-115N4.1 expression was detected in both lymphocytes and monocytes of human peripheral blood, and in vitro overexpression of RP11-115N4.1 decreased cell proliferation in K562 cells significantly. Furthermore, heat-shock HSP70 genes (HSPA1A and HSPA1B) were found to be significantly upregulated upon RP11-115N4.1 overexpression by transcriptome analysis (HSPA1A (P = 4.39E-08, Fold change = 4.17), HSPA1B (P = 2.26E-06, Fold change = 2.99)). RNA pull down and RNA immunoprecipitation assay (RIP) analysis demonstrated that RP11-115N4.1 bound to HNRNPH3 protein directly, which in turn activate heat-shock proteins (HSP70) analyzed by protein-protein interaction and HNRNPH3 knockdown assays. Most importantly, the high expression of HSP70 was also verified in the serum of URSA patients and the supernatant of K562 cells with RP11-115N4.1 activation, and HSP70 in supernatant can exacerbate inflammatory responses in monocytes by inducing IL-6, IL-1β, and TNF-α and inhibit the migration of trophoblast cells, which might associate with URSA.

Conclusion

Our results demonstrated that the activation of RP11-115N4.1 can significantly increase the protein level of HSP70 via binding to HNRNPH3, which may modulate the immune responses and related to URSA. Moreover, RP11-115N4.1 may be a novel etiological biomarker and a new therapeutic target for URSA."xsd:string
http://purl.uniprot.org/citations/34484222http://purl.org/dc/terms/identifier"doi:10.3389/fimmu.2021.717785"xsd:string
http://purl.uniprot.org/citations/34484222http://purl.uniprot.org/core/author"Chen H."xsd:string
http://purl.uniprot.org/citations/34484222http://purl.uniprot.org/core/author"Cao C."xsd:string
http://purl.uniprot.org/citations/34484222http://purl.uniprot.org/core/author"Luo Y."xsd:string
http://purl.uniprot.org/citations/34484222http://purl.uniprot.org/core/author"Liu M."xsd:string
http://purl.uniprot.org/citations/34484222http://purl.uniprot.org/core/author"Huang B."xsd:string
http://purl.uniprot.org/citations/34484222http://purl.uniprot.org/core/author"Sun X."xsd:string
http://purl.uniprot.org/citations/34484222http://purl.uniprot.org/core/author"Wang D."xsd:string
http://purl.uniprot.org/citations/34484222http://purl.uniprot.org/core/author"Zhang J."xsd:string
http://purl.uniprot.org/citations/34484222http://purl.uniprot.org/core/author"Zhu L."xsd:string
http://purl.uniprot.org/citations/34484222http://purl.uniprot.org/core/author"Nie X."xsd:string
http://purl.uniprot.org/citations/34484222http://purl.uniprot.org/core/author"Hu L."xsd:string
http://purl.uniprot.org/citations/34484222http://purl.uniprot.org/core/author"Mo H."xsd:string
http://purl.uniprot.org/citations/34484222http://purl.uniprot.org/core/author"Zhong X."xsd:string
http://purl.uniprot.org/citations/34484222http://purl.uniprot.org/core/author"Zhu M."xsd:string
http://purl.uniprot.org/citations/34484222http://purl.uniprot.org/core/author"Yi J."xsd:string
http://purl.uniprot.org/citations/34484222http://purl.uniprot.org/core/author"Liang L."xsd:string
http://purl.uniprot.org/citations/34484222http://purl.uniprot.org/core/author"Deng K."xsd:string
http://purl.uniprot.org/citations/34484222http://purl.uniprot.org/core/author"Du T."xsd:string
http://purl.uniprot.org/citations/34484222http://purl.uniprot.org/core/date"2021"xsd:gYear
http://purl.uniprot.org/citations/34484222http://purl.uniprot.org/core/name"Front Immunol"xsd:string
http://purl.uniprot.org/citations/34484222http://purl.uniprot.org/core/pages"717785"xsd:string
http://purl.uniprot.org/citations/34484222http://purl.uniprot.org/core/title"Long Noncoding RNA RP11-115N4.1 Promotes Inflammatory Responses by Interacting With HNRNPH3 and Enhancing the Transcription of HSP70 in Unexplained Recurrent Spontaneous Abortion."xsd:string
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