Long non coding RNA SLC26A4‐AS1 exerts antiangiogenic effects in human glioma by upregulating NPTX1 via NFKB1 transcriptional factor

Metastasis accounts for poor prognosis of cancers and related deaths. Accumulating evidence has shown that long noncoding RNAs (lncRNAs) play critical roles in several types of cancer. However, which lncRNAs contribute to metastasis of colon cancer is still largely unknown. In this study, we found that lncRNA LINC01578 was correlated with metastasis and poor prognosis of colon cancer. LINC01578 was upregulated in colon cancer, associated with metastasis, advanced clinical stages, poor overall survival, disease-specific survival, and disease-free survival. Gain-of-function and loss-of-function assays revealed that LINC01578 enhanced colon cancer cell viability and mobility in vitro and colon cancer liver metastasis in vivo. Mechanistically, nuclear factor kappa B (NF-jB) and Yin Yang 1 (YY1) directly bound to the LINC01578 promoter, enhanced its activity, and activated LINC01578 expression. LINC01578 was shown to be a chromatin-bound lncRNA, which directly bound NFKBIB promoter. Furthermore, LINC01578 interacted with and recruited EZH2 to NFKBIB promoter and further repressed NFKBIB expression, thereby activating NF-jB signaling. Through activation of NF-jB, LINC01578 further upregulated YY1 expression. Through activation of the NF-jB/YY1 axis, LINC01578 in turn enhanced its own promoter activity, suggesting that LINC01578 and NF-jB/YY1 formed a positive feedback loop. Blocking NF-jB signaling abolished the oncogenic roles of LINC01578 in colon cancer. Furthermore, the expression levels of LINC01578, NFKBIB, and YY1 were correlated in clinical tissues. Collectively, this study demonstrated that LINC01578 promoted colon cancer metastasis via forming a positive feedback loop with NF-jB/YY1 and suggested that LINC01578 represents a potential prognostic biomarker and therapeutic target for colon cancer metastasis.

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“…The mechanisms exerted by lncRNAs are complicated [46][47][48]. Different subcellular locations of lncRNAs influence their mechanisms of action.…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA LINC01578 drives colon cancer metastasis through a positive feedback loop with the NF‐κB/YY1 axis

et al. 2020

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“…It has recently been found that multiple long non-coding RNAs (lncRNAs) are involved in a wide range of biological functions, including angiogenesis, through the regulation of gene expression in cancer [56]. SLC26A4-AS1 lncRNA has been reported to promote NPTX1 transcriptional activity by recruiting nuclear factor kappa B 1 (NF-κB 1), which has an anti-angiogenic effect on glioma cells; the problem is that SLC26A4-AS1 expression is suppressed in glioma cells.…”

Section: Heterogeneitymentioning

confidence: 99%

Molecular Mechanisms of Drug Resistance in Glioblastoma

Дымова

Kuligina

Richter

2021

IJMS

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Glioblastoma multiforme (GBM) is the most common and fatal primary brain tumor, is highly resistant to conventional radiation and chemotherapy, and is not amenable to effective surgical resection. The present review summarizes recent advances in our understanding of the molecular mechanisms of therapeutic resistance of GBM to already known drugs, the molecular characteristics of glioblastoma cells, and the barriers in the brain that underlie drug resistance. We also discuss the progress that has been made in the development of new targeted drugs for glioblastoma, as well as advances in drug delivery across the blood–brain barrier (BBB) and blood–brain tumor barrier (BBTB).

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“…An inflammatory cytokine that promotes EMT and invasiveness of cancer cells. SLC26A4-AS1 promotes the transcriptional activity of NPTX1 by recruiting NFKB1, thereby producing antiangiogenic effects on glioma cells (32). The platelet subtype of phosphofructokinase (PFKP) is a rate-limiting enzyme involved in glycolysis.…”

Section: A B C Dmentioning

confidence: 99%

Characteristics of hypoxic tumor microenvironment in non-small cell lung cancer, involving molecular patterns and prognostic signature

Huang¹,

Wang²,

Zhang³

et al. 2021

Transl Lung Cancer Res

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Background: The mechanisms of hypoxia or immune microenvironment in cancer have been studiedrespectively, but the role of hypoxia immune microenvironment in non-small cell lung cancer (NSCLC) still needs further exploration.Methods: By applying the K-means algorithm, 1,121 patients with NSCLC were divided into three categories. We evaluated the constructed signature in order to link it with the prognosis, which was constructed by univariate and least absolute shrinkage operator (LASSO) Cox regression analysis.Results: A total of three clusters were obtained by clustering five Gene Expression Omnibus (GEO) data sets. Gene Set Variation Analysis (GSVA) and immune infiltration analysis were performed to explore the biological behavior. Cluster one presented an activated state of oncogenic pathways, and compared with the other two clusters, the median risk score was the highest, which was the reason for its poor survival. Cluster three showed that the immune pathway was active and the median risk score was the lowest, so the survival was the best. However, cluster two presented a state in which both immune and matrix pathways were activate. This was manifested as mutual antagonism, and its risk score was in the middle. Its survival was in the middle.Conclusions: This work revealed the role of hypoxia related genes (HRGs) modification in tumor microenvironment, which was conducive to our comprehensive analysis of the prognosis of NSCLC, and provided direction and guidance for clinical immunotherapy.

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Long non coding RNA SLC26A4‐AS1 exerts antiangiogenic effects in human glioma by upregulating NPTX1 via NFKB1 transcriptional factor

Cited by 38 publications

References 30 publications

Long noncoding RNA LINC01578 drives colon cancer metastasis through a positive feedback loop with the NF‐κB/YY1 axis

Long noncoding RNA LINC01578 drives colon cancer metastasis through a positive feedback loop with the NF‐κB/YY1 axis

Molecular Mechanisms of Drug Resistance in Glioblastoma

Characteristics of hypoxic tumor microenvironment in non-small cell lung cancer, involving molecular patterns and prognostic signature

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