Galectin-3 activates TLR4/NF-κB signaling to promote lung adenocarcinoma cell proliferation through activating lncRNA-NEAT1 expression

Wu, Zhou; Chen, Xing; Hu, Qinghua; Chen, Xuliang; Chen, Yingji; Huang, Lei

doi:10.1186/s12885-018-4461-z

Cited by 96 publications

(86 citation statements)

References 40 publications

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“…Mechanistically, upregulation of NEAT1 in GSCs under ADV infection could be attributed to TLR9 activation, and knockdown of NEAT1 was accompanied with an inhibition of STAT3 expression and phosphorylation. This is consistent with several reports showing that NEAT1 promotes cancer progression by enhancing STAT3 signaling [48][49][50] . Therefore, ADV infection likely triggers TLR9/MYD88 signaling, which upregulated NEAT1 and activated STAT3, and activated STAT3 further upregulates NEAT1 to form a positivefeedback loop, and promotes GSCs formation from primary glioma cells.…”

Section: Discussionsupporting

confidence: 93%

“…On the other hand, transfection of NEAT1 siRNA abrogated the increased levels of STAT3 and phosphorylated STAT3 induced by ADV infection (Figure 6C, 6D, supplementary Figure S4F). These results, in combination with literatures, suggested that NEAT1 is downstream to TLR9-MYD88 and regulates STAT3 46,[48][49][50] .…”

Section: Neat1 Is Associated With Activation Of Tlr-stat Pathway In Gbmsupporting

confidence: 84%

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Adenovirus infection promotes the formation of glioma stem cells from glioblastoma cells through the TLR9/NEAT1/STAT3 pathway

Zang

Zheng

Cao

et al. 2020

Preprint

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Background Glioma stem cells (GSCs) are glioma cells with stemness and are responsible for a variety of malignant behaviors of glioma. Evidence has shown that signals from tumor microenvironment (TME) enhance stemness of glioma cells. However, identification of the signaling molecules and underlying mechanisms has not been completely elucidated. Methods Human samples and glioma cell lines were cultured in vitro to determine the effects of adenovirus (ADV) infection by sphere formation, RT-qPCR, western blotting, FACS and immunofluorescence. For in vivo analysis, mouse intracranial tumor model was applied. Bioinformatics analysis, gene knockdown by siRNA, RT-qPCR and western blotting were applied for further mechanistic studies. Results Infection of patient-derived glioma cells with ADV increases the formation of tumor spheres. ADV infection upregulated stem cell markers and in turn promoted the capacities of self-renewal and multi-lineage differentiation of the infected tumor spheres. These ADV infected tumor spheres had stronger potential to form xenograft tumors in immune-compromised mice. GSCs formation could be promoted by ADV infection via TLR9, because TLR9 was upregulated after ADV infection, and knockdown of TLR9 reduced ADV-induced GSCs. Consistently, MYD88, as well as total STAT3 and phosphorylated (p-)STAT3, were also upregulated in ADV-induced GSCs. Knockdown of MYD88 or pharmaceutical inhibition of STAT3 attenuated stemness of ADV-induced GSCs. Moreover, we found that ADV infection upregulated lncRNA NEAT1. Knockdown of NEAT1 impaired stemness of ADV-induced GSCs. Lastly, HMGB1, a damage associated molecular pattern (DAMP) that triggers TLR signaling, also upregulated stemness markers in glioma cells. Conclusion ADV, which has been developed as vectors for gene therapy and oncolytic virus, promotes the formation of GSCs via TLR9/NEAT1/STAT3 signaling.

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Section: Discussionsupporting

confidence: 93%

Section: Neat1 Is Associated With Activation Of Tlr-stat Pathway In Gbmsupporting

confidence: 84%

Adenovirus infection promotes the formation of glioma stem cells from glioblastoma cells through the TLR9/NEAT1/STAT3 pathway

Zang

Zheng

Cao

et al. 2020

Preprint

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“…5). Lgals3, encoding Galectin-3 that can activate TLR4/NF-κB signaling, was induced peaking at day 3-14 [23].…”

Section: Dampsmentioning

confidence: 99%

Temporal expression profiling of DAMPs-related genes revealed the biphasic post-ischemic inflammation in the experimental stroke model

et al. 2020

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The neuroinflammation in the ischemic brain could occur as sterile inflammation in response to damage-associated molecular patterns (DAMPs). However, its long-term dynamic transcriptional changes remain poorly understood. It is also unknown whether this neuroinflammation contributes to the recovery or just deteriorates the outcome. The purpose of this study is to characterize the temporal transcriptional changes in the post-stroke brain focusing on DAMPs-related genes by RNA-sequencing during the period of 28 days. We conducted the RNA-sequencing on day 1, 3, 7, 14, 28 post-stroke in the mouse photothrombosis model. The gross morphological observation showed the ischemic lesion on the ipsilateral cortex turned into a scar with the clearance of cellular debris by day 28. The transcriptome analyses indicated that post-stroke period of 28 days was classified into four categories (I Baseline, II Acute, III Sub-acute-#1, IV Sub-acute-#2 phase). During this period, the well-known genes for DAMPs, receptors, downstream cascades, pro-inflammatory cytokines, and phagocytosis were transcriptionally increased. The gene ontology (GO) analysis of biological process indicated that differentially expressed genes (DEGs) are genetically programmed to achieve immune and inflammatory pathways. Interestingly, we found the biphasic induction of various genes, including DAMPs and pro-inflammatory factors, peaking at acute and sub-acute phases. At the subacute phase, we also observed the induction of genes for phagocytosis as well as regulatory and growth factors. Further, we found the activation of CREB (cAMP-response element binding protein), one of the key players for neuronal plasticity, in peri-ischemic neurons by immunohistochemistry at this phase. Taken together, these findings raise the possibility the recurrent inflammation occurs at the sub-acute phase in the post-stroke brain, which could be involved in the debris clearance as well as neural reorganization.

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“…Nuclear enriched abundant transcript 1 (NEAT1) is a lncRNA transcribed from the diverse endocrinal neoplasia locus [10]. The interaction of lncRNA NEAT1 has been documented in glioma, prostate cancer and lung adenocarcinoma [11][12][13].LncRNA NEAT1 was also suggested as a tumor promotor in OS by several studies [14][15][16].MicroRNAs (miRNAs) are tiny (~ 22 nucleotides) endogenous non-coding RNA molecules which act at the post-transcriptional level and regulate mRNA expression [17]. They are involved in multiple complicated cellular behaviors [18].…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Long noncoding RNA NEAT1 aggravates osteosarcoma carcinogenesis via regulating the microRNA-579/MMP13 axis

Wang

Zhou

Zhang

et al. 2020

Preprint

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Background: Previous studies have suggested that long non-coding RNAs (lncRNAs) were involved in tumorigenesis in various human carcinomas, including osteosarcoma (OS). However, the expression and specific role of lncRNA NEAT1 in OS remain unknown. The current study aimed at revealing the role of lncRNA NEAT1 and its related mechanism in OS.Methods: Expression profiles of lncRNAs in OS tissues were constructed, and lncRNA NEAT1 expression was verified with RT-qPCR followed by sub-localization. LncRNA-microRNA (miRNA) and miRNA-mRNA interactions were predicted. Validation was performed using dual luciferase reporter gene assay, and gain-and loss-of-function experiments. The effects of lncRNA NEAT1, miR-579 and MMP13 on the proliferation, migration and invasion, epithelial-mesenchymal transition (EMT) of OS cells were detected using colony formation, cell counting kit-8 (CCK-8), Transwell assays and Western blot analysis. Results: LncRNA NEAT1 overexpression was observed in OS tissues and cell lines which located in the cytoplasm. Transfection-induced downregulation of lncRNA NEAT1/MMP13 or overexpression of miR-579 blocked the progression of OS cells. LncRNA NEAT1 promotes MMP13 through sponging miR-579.Conclusion: LncRNA NEAT1 might be beneficial for OS aggravation via sponging miR-579 and facilitating MMP13 expression, which represents a candidate marker and target for OS therapy.clarify the invisible mechanism underlying tumorigenesis and to develop novel molecular targets of OS.Long non-coding RNAs (lncRNAs), surpassing over 200 nucleotides in length, are a prominent class of RNAs exerting a crucial regulatory potential in tumor cell behaviors [6]. Increasing evidence has illustrated that aberrantly expressed lncRNAs were highly associated with the occurrence and development of many human malignancies, including OS [7-9]. Nuclear enriched abundant transcript 1 (NEAT1) is a lncRNA transcribed from the diverse endocrinal neoplasia locus [10]. The interaction of lncRNA NEAT1 has been documented in glioma, prostate cancer and lung adenocarcinoma [11][12][13].LncRNA NEAT1 was also suggested as a tumor promotor in OS by several studies [14][15][16].MicroRNAs (miRNAs) are tiny (~ 22 nucleotides) endogenous non-coding RNA molecules which act at the post-transcriptional level and regulate mRNA expression [17]. They are involved in multiple complicated cellular behaviors [18]. Importantly, emerging evidence has pointed out that miRNAs participate in OS, such as miR-18a-5p, miR-671-5p, miR-1301, and miR-212 [19-22]. MiR-579 was reported to be associated with malignancies, such as breast cancer, ovarian cancer, and human glioblastoma [23][24][25]. However, its function in OS deserves further studies.LncRNAs are proved to serve as competing endogenous RNAs (ceRNAs), which sponges certain miRNAs to mediate its target gene, thus changing the post-transcriptional regulation [1]. However, the concrete influence that lncRNA NEAT1 and miR-579 exerts on OS, especially their interaction is still to be elucidated. In this experimen...

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Galectin-3 activates TLR4/NF-κB signaling to promote lung adenocarcinoma cell proliferation through activating lncRNA-NEAT1 expression

Cited by 96 publications

References 40 publications

Adenovirus infection promotes the formation of glioma stem cells from glioblastoma cells through the TLR9/NEAT1/STAT3 pathway

Adenovirus infection promotes the formation of glioma stem cells from glioblastoma cells through the TLR9/NEAT1/STAT3 pathway

Temporal expression profiling of DAMPs-related genes revealed the biphasic post-ischemic inflammation in the experimental stroke model

Long noncoding RNA NEAT1 aggravates osteosarcoma carcinogenesis via regulating the microRNA-579/MMP13 axis

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