Positive Feedback Loop of Long Noncoding RNA OASL-IT1 and Innate Immune Response Restricts the Replication of Zika Virus in Epithelial A549 Cells

Expression of host noncoding RNAs and coding mRNAs is significantly altered by viral infection. In the current study, we screened the transcriptional profile of human lung epithelial A549 cells infected with Zika virus (ZIKV) by microarray assay. Seventy-nine long noncoding RNAs (lncRNAs) and 140 mRNAs were differentially expressed (DE). The bioinformatics analysis revealed that the mRNAs adjacent to the DE lncRNAs were closely related to the host responses to viral infection. We selected 7 lncRNAs from the top 50 hits for validation. The quantitative real-time PCR data confirmed that expression of selected lncRNAs was induced by ZIKV infection. Moreover, the expression of 7 lncRNAs was induced by infection of dengue virus, Japanese encephalitis virus, or vesicular stomatitis virus, or by treatment of poly(I:C) and IFN-β. Furthermore, loss of innate immune adaptor IPS-1 or receptor IFNAR1 resulted in lower induction levels of several lncRNAs by ZIKV. Overexpression of 3 lncRNAs (RPL27-OT1, OASL-IT1, and REC8-OT3) reduced the virus yields of ZIKV. Knockout of OASL-IT1 significantly enhanced ZIKV replication. In OASL-IT1 knockout cells, the levels of interferons (IFNs) and the activation of 3 innate immune signaling pathways triggered by ZIKV were dramatically reduced. Collectively, our work found a positive feedback loop in the IFN system, in which IFNs and OASL-IT1 regulate each other, thereby promoting establishment of antiviral defense.

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IL-18 Levels and the Outcome of Innate Immune Response to Lipopolysaccharide: Importance of a Positive Feedback Loop with Caspase-1 in IL-18 Expression

The Journal of Immunology ◽

10.4049/jimmunol.169.5.2536 ◽

2002 ◽

Vol 169 (5) ◽

pp. 2536-2544 ◽

Cited By ~ 23

Author(s):

Vishwas D. Joshi ◽

Dhananjaya V. Kalvakolanu ◽

Jeffrey D. Hasday ◽

Richard J. Hebel ◽

Alan S. Cross

Keyword(s):

Immune Response ◽

Innate Immune Response ◽

Positive Feedback ◽

Feedback Loop ◽

Innate Immune ◽

Positive Feedback Loop ◽

Caspase 1

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An HGF-dependent positive feedback loop between bladder cancer cells and fibroblasts mediates lymphangiogenesis and lymphatic metastasis

10.21203/rs.3.rs-1104668/v1 ◽

2021 ◽

Author(s):

Changhao Chen ◽

Yuting Li ◽

Yuming Luo ◽

Hanhao Zheng ◽

Yan Lin ◽

...

Keyword(s):

Bladder Cancer ◽

Cancer Cells ◽

Positive Feedback ◽

Noncoding Rna ◽

Feedback Loop ◽

Xenograft Model ◽

Positive Feedback Loop ◽

Reciprocal Interactions ◽

Orthotopic Xenograft Model ◽

Bladder Cancer Cells

Abstract Cancer-associated fibroblasts (CAFs) are essential etiologic actors in promoting tumor progression via extensive reciprocal interactions with cancer cells. Yet, the biological role and regulatory mechanism of CAFs phenotype underlying lymph node (LN) metastasis of bladder cancer (BCa) remain unclear. Here, we report that BCa cell-secreted extracellular vesicles (EVs) played an important role in the CAF-enriched microenvironment, which correlated with BCa lymphangiogenesis and LN metastasis. RNA sequencing identified an EV-associated long noncoding RNA, LINC00665, which acted as a crucial mediator of CAF infiltration in BCa. LINC00665 mediated EV release from BCa cells to endow fibroblasts with the CAF phenotype, which reciprocally induced LINC00665 upregulation to form a RAB27B-HGF-c-Myc positive feedback loop, facilitating BCa lymphangiogenesis and LN metastasis. Importantly, we demonstrate that Cabozantinib significantly suppressed LINC00665-mediated BCa LN metastasis in an orthotopic xenograft model. Our study highlights a molecular mechanism by which LINC00665 induces a RAB27B-HGF-c-Myc positive feedback loop between cancer cells and fibroblasts to sustain BCa LN metastasis, and represents LINC00665 as a potential therapeutic target in BCa LN metastasis.

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Long noncoding RNA CASC9/miR-519d/STAT3 positive feedback loop facilitate the glioma tumourigenesis

Journal of Cellular and Molecular Medicine ◽

10.1111/jcmm.13932 ◽

2018 ◽

Vol 22 (12) ◽

pp. 6338-6344 ◽

Cited By ~ 22

Author(s):

Hongjiang Liu ◽

Chen Li ◽

Jiankai Yang ◽

Yuchen Sun ◽

Shunyao Zhang ◽

...

Keyword(s):

Positive Feedback ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Feedback Loop ◽

Positive Feedback Loop

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LncRNA Snhg1-driven self-reinforcing regulatory network promotes cardiomyocyte cytokinesis and improves cardiac function

10.1101/2020.10.26.354613 ◽

2020 ◽

Author(s):

Mengsha Li ◽

Hao zheng ◽

Yijin Chen ◽

Bing Li ◽

Guojun Chen ◽

...

Keyword(s):

Myocardial Infarction ◽

Cell Division ◽

Cardiac Function ◽

Positive Feedback ◽

Noncoding Rna ◽

Feedback Loop ◽

Feedback Loops ◽

Positive Feedback Loop ◽

Proliferative Effect ◽

Regenerative Approach

AbstractMost of current cardiac regenerative approaches result in very limited cell division. Positive feedback loops are vital for cell division, but their role in CM regeneration remains unclear. We aimed to demonstrate that lncRNA Snhg1 formed a positive feedback loop with c-Myc to induce stable CM cytokinesis. We found that Snhg1 expression was increased in human and mouse fetal and myocardial infarction (MI) hearts, particularly in CMs. Snhg1 overexpression elicited stable CM proliferation and improved post-MI cardiac function. Antagonism of Snhg1 in neonatal mice inhibited CM proliferation and impaired cardiac repair after MI. Proliferative effect was confirmed using cardiac-specific transgenic mice. RNA pull-down assays showed that Snhg1 directly bound to PTEN and activated PI3K-Akt pathway, resulting in c-Myc activation. Chromatin immunoprecipitation experiments showed that Snhg1 expression was upregulated by c-Myc binding to the Snhg1 promoter region, indicating a positive feedback loop between c-Myc and Snhg1. In conclusion, c-Myc/Snhg1/PI3k-Akt positive feedback loop drove sustained activation of cell cycle re-entry and induced stable CM cytokinesis, and thus may be an attractive strategy for promoting heart regenerative response.Clinical PerspectivesMost of the current cardiac regenerative approaches result in very limited cell division and little new cardiomyocyte (CM) mass. Positive feedback loops are vital for cell division, but their role in CM regeneration remain unclear. Here, we identified the long noncoding RNA Snhg1 as a driver to induce stable CM division and improve cardiac function after myocardial infarction (MI) by forming a positive feedback loop to sustain PI3K-Akt signaling activation. This finding might provide a novel therapeutic of Snhg1 as a promising regenerative approach to improve the prognosis of patients with heart failure.

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Long Noncoding RNA HCG18 Promotes Malignant Phenotypes of Breast Cancer Cells via the HCG18/miR-103a-3p/UBE2O/mTORC1/HIF-1α–Positive Feedback Loop

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.675082 ◽

2021 ◽

Vol 9 ◽

Author(s):

Xu Liu ◽

Kun Qiao ◽

Kaiyuan Zhu ◽

Xianglan Li ◽

Chunbo Zhao ◽

...

Keyword(s):

Breast Cancer ◽

Positive Feedback ◽

Noncoding Rna ◽

Feedback Loop ◽

Hypoxia Inducible Factor ◽

The Cancer Genome Atlas ◽

Positive Feedback Loop ◽

Downstream Target

In recent years, an increasing number of studies have reported that long noncoding RNAs (lncRNAs) play crucial roles in breast cancer (BC) progression and metastasis. Another study group of our research center reported that lncRNA HCG18 was one of the 30 upregulated lncRNAs in BC tissues compared with normal tissues in The Cancer Genome Atlas database. However, the exact biological roles of HCG18 in BC remain unclear. In this study, we demonstrated that HCG18 is significantly upregulated in BC tissues and cells and that BC patients with high HCG18 expression tend to have poor prognosis. In vitro assays indicated that HCG18 promotes BC cell proliferation and invasion and endows BC cells with cancer stemness properties. In vivo assays revealed that reducing HCG18 expression in the BC cell line MDA-MB-231 markedly decreased tumor growth and lung metastasis in xenograft mouse models. In terms of mechanism, we found that HCG18 positively regulated the expression of BC-related ubiquitin-conjugating enzyme E2O (UBE2O) by sponging miR-103a-3p, and our previous research verified that UBE2O could promote the malignant phenotypes of BC cells through the UBE2O/AMPKα2/mTORC1 axis. Furthermore, as a downstream target of the HCG18/miR-103a-3p/UBE2O/mTORC1 axis, hypoxia-inducible factor 1α transcriptionally promoted HCG18 expression and then formed a positive feedback loop in BC. Taken together, these results confirm that HCG18 plays an oncogenic role in BC and might serve as a prognostic biomarker and a potential therapeutic target for BC treatment.

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Long noncoding RNA HEGBC promotes tumorigenesis and metastasis of gallbladder cancer via forming a positive feedback loop with IL-11/STAT3 signaling pathway

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-018-0847-7 ◽

2018 ◽

Vol 37 (1) ◽

Cited By ~ 11

Author(s):

Liang Yang ◽

Qingxiang Gao ◽

Xiaoxiong Wu ◽

Feiling Feng ◽

Kaiyun Xu

Keyword(s):

Gallbladder Cancer ◽

Signaling Pathway ◽

Positive Feedback ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Feedback Loop ◽

Positive Feedback Loop ◽

Stat3 Signaling ◽

Stat3 Signaling Pathway

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A Positive Feedback Loop of Long Noncoding RNA LINC00152 and KLF5 Facilitates Breast Cancer Growth

Frontiers in Oncology ◽

10.3389/fonc.2021.619915 ◽

2021 ◽

Vol 11 ◽

Author(s):

Qiang Li ◽

Xiao Wang ◽

Liheng Zhou ◽

Mingyun Jiang ◽

Guansheng Zhong ◽

...

Keyword(s):

Breast Cancer ◽

Positive Feedback ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Feedback Loop ◽

Clinical Value ◽

Survival Prognosis ◽

Aberrant Expression ◽

Positive Feedback Loop

The long noncoding RNA (lncRNA) LINC00152, also known as CYTOR, displays aberrant expression in various cancers. However, its clinical value and functional mechanisms in breast cancer remain insufficiently understood. Our study found that LINC00152 is significantly upregulated in breast cancer, and that it acts as an indicator of poor survival prognosis. Further studies revealed that LINC00152 knockdown suppresses cell proliferation and tumorigenicity in vitro and in vivo. Mechanistic analyses demonstrated that LINC00152 directly binds to KLF5 protein and increases KLF5 stability. Moreover, LINC00152 is also a KLF5-responsive lncRNA, and KLF5 activates LINC00152 transcription by directly binding to its promoter. Our study suggests that LINC00152 promotes tumor progression by interacting with KLF5. LINC00152 may be a valuable prognostic predictor for breast cancer, and the positive feedback loop of LINC00152-KLF5 could be a therapeutic target in pharmacological strategies.

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