Inducible degradation of lncRNA Sros1 promotes IFN-γ-mediated activation of innate immune responses by stabilizing Stat1 mRNA

Xu, Huijing; Jiang, Yan; Xu, Xiaoqing; Su, Xiaoping; Liu, Yang; Ma, Yuanwu; Zhao, Yong; Shen, Zhongyang; Huang, Bo; Cao, Xuetao

doi:10.1038/s41590-019-0542-7

Cited by 100 publications

(79 citation statements)

References 48 publications

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“…Studies have also shown that silencing the lncRNA CEBPA-AS1 can regulate OSCC cell proliferation, cell apoptosis, migration, and invasion by targeting CEBPA and via a novel pathway, CEBPA/Bcl2 (30). Similarly, abundant studies demonstrated that E2F4, STAT1, MYC, ERG, and NFYB may play an important role in the pathogenesis and progression of various cancers, including OSCC, and the underlying mechanism may be related to dysregulated lncRNA (31)(32)(33)(34)(35)(36)(37). All of these studies confirm that the TFs screened in our research play a critical role in tumor pathogenesis.…”

Section: Discussionmentioning

confidence: 98%

Analysis of Differentially Expressed Long Non-coding RNAs and the Associated TF-mRNA Network in Tongue Squamous Cell Carcinoma

et al. 2020

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Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play crucial roles in tongue squamous cell carcinoma (TSCC) tumorigenesis. However, the comprehensive regulation of lncRNAs-transcription factors (TFs)-messenger RNAs (mRNAs) in TSCC remains largely unknown. The purpose of this study was to identify aberrantly expressed lncRNAs and the associated TF-mRNA network in TSCC. To explore lncRNA and mRNA expression profiles and their biological functions in TSCC, we surveyed the lncRNA and mRNA expression profiles of TSCC and adjacent tissues using next-generation RNA sequencing in six patients. Thousands of significantly differentially expressed lncRNAs (DELs) and mRNAs (DEGs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to demonstrate the principal functions of the significantly dysregulated lncRNAs and genes. A total of 40 DELs were screened between TSCC and adjacent non-cancerous tissues. Results obtained from GEPIA and StarBase confirmed the expression levels of nine pivotal DELs obtained in our study. Three of the nine deregulated DELs were identified to have a significant impact on the overall survival of TSCC patients, which were evaluated with GEPIA and StarBase. LncMAP was used to predict the lncRNA-TF-mRNA triplets in TSCC. Furthermore, based on these results, we established lncRNA-TF-mRNA coexpression networks for the up-and downregulated lncRNAs using Cytoscape. We also found that among the nine pivotal lncRNAs, there is limited research on the abnormally expressed lncRNAs, including RP11-54H7.4, CTD-2545M3.8, RP11-760H22.2, RP4-791M13.3, and LINC01405, in TSCC pathogenesis. This is the first study to show that RP11-54H7.4, LINC00152, and LINC01405 can be acted as a prognostic target for TSCC. Our findings provide a novel perspective and lay the foundation for future research on the potential roles of lncRNAs, TFs, and mRNAs in TSCC. Verification of the potential lncRNA-TF-mRNA regulatory networks will provide a more comprehensive understanding of the pathogenesis of TSCC.

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Section: Discussionmentioning

confidence: 98%

Analysis of Differentially Expressed Long Non-coding RNAs and the Associated TF-mRNA Network in Tongue Squamous Cell Carcinoma

et al. 2020

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“…Characterizing the epigenetic landscape of genes encoding lncRNAs identifies a lncRNA EPIC1 , which promotes cancer cell-cycle progression by interacting with MYC, thus enhancing MYC occupancy on target genes 23 . Up to date, numerous experimental evidences have shown that the competition for miRNAs plays an integral part in the regulation of both lncRNAs and mRNAs 8 , 24 . Although the diverse functions of lncRNA have been characterized, the influence of lncRNAs on the stemness of cancer stem cells has still poorly understood.…”

Section: Discussionmentioning

confidence: 99%

LncRNA LHFPL3-AS1 contributes to tumorigenesis of melanoma stem cells via the miR-181a-5p/BCL2 pathway

2020

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Long noncoding RNAs (lncRNAs) are recognized as a new area for cancer therapy. B-cell lymphoma-2 (Bcl-2)-mediated suppression of apoptosis is an important molecular hallmark of cancer. However, the influence of lncRNA on the regulation of oncogenic Bcl-2 in cancer stem cells has not been explored. In this study, our findings revealed that the lncRNA LHFPL3-AS1-long, generated from the polypyrimidine tract binding protein 1 (PTBP1)-mediated splicing of the LHFPL3-AS1 precursor, upregulated BCL2 protein to contribute to tumorigenesis of melanoma stem cells. The in vitro and in vivo results showed that LHFPL3-AS1-long directly interacted with miR-181a-5p to inhibit the mRNA degradation of Bcl-2 (the target of miR-181), thus suppressing apoptosis of melanoma stem cells. The splicing factor PTBP1 regulated the alternative splicing of LHFPL3-AS1 transcript by preferentially binding to the motifs located in exon3 of LHFPL3-AS1 precursor, leading to the biogenesis of LHFPL3-AS1-long in melanoma stem cells. In patients with melanoma, the expressions of PTBP1 and LHFPL3-AS1 were significantly upregulated compared with the healthy donors. Therefore, our study revealed a mechanistic crosstalk among an onco-splicing factor, lncRNA and tumorigenesis of melanoma stem cells, enabling PTBP1 and LHFPL3-AS1 to serve as the attractive therapeutic targets for melanoma.

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“…Mechanistically, p(I:C) induction increases the translocation of lnc13 from the nucleus to the cytoplasm, where it favors STAT1 mRNA binding to poly(rC) binding protein 2 (PCBP2) and results in increased STAT1 mRNA stability. In the same line, lncRNA Sros1 blocks the binding between STAT1 mRNA and cell cycle-associated protein 1 (CAPRIN1), which contributes to STAT1 mRNA stabilization and signaling [158]. Although Sros1 activity has been described after stimulation with IFN-γ, it could also regulate STAT1 expression in the context of type I IFN signaling.…”

Section: Lncrnas Are Involved In Ifn Signalingmentioning

confidence: 99%

LncRNAs in the Type I Interferon Antiviral Response

Suarez

Prats-Mari

Unfried

et al. 2020

IJMS

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The proper functioning of the immune system requires a robust control over a delicate equilibrium between an ineffective response and immune overactivation. Poor responses to viral insults may lead to chronic or overwhelming infection, whereas unrestrained activation can cause autoimmune diseases and cancer. Control over the magnitude and duration of the antiviral immune response is exerted by a finely tuned positive or negative regulation at the DNA, RNA, and protein level of members of the type I interferon (IFN) signaling pathways and on the expression and activity of antiviral and proinflammatory factors. As summarized in this review, committed research during the last decade has shown that several of these processes are exquisitely regulated by long non-coding RNAs (lncRNAs), transcripts with poor coding capacity, but highly versatile functions. After infection, viruses, and the antiviral response they trigger, deregulate the expression of a subset of specific lncRNAs that function to promote or repress viral replication by inactivating or potentiating the antiviral response, respectively. These IFN-related lncRNAs are also highly tissue- and cell-type-specific, rendering them as promising biomarkers or therapeutic candidates to modulate specific stages of the antiviral immune response with fewer adverse effects.

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Inducible degradation of lncRNA Sros1 promotes IFN-γ-mediated activation of innate immune responses by stabilizing Stat1 mRNA

Cited by 100 publications

References 48 publications

Analysis of Differentially Expressed Long Non-coding RNAs and the Associated TF-mRNA Network in Tongue Squamous Cell Carcinoma

Analysis of Differentially Expressed Long Non-coding RNAs and the Associated TF-mRNA Network in Tongue Squamous Cell Carcinoma

LncRNA LHFPL3-AS1 contributes to tumorigenesis of melanoma stem cells via the miR-181a-5p/BCL2 pathway

LncRNAs in the Type I Interferon Antiviral Response

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