Aberrant methylation-mediated downregulation of long noncoding RNA LOC100130476 correlates with malignant progression of esophageal squamous cell carcinoma

Guo, Wei; Zhao, Dong; Ya-bin, Shi; Liu, Shengnan; Liang, Jia; Guo, Yanli; Guo, Xin; Shen, Supeng; Shan, Baoen

doi:10.1016/j.dld.2016.05.010

Cited by 21 publications

(15 citation statements)

References 34 publications

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“…Moreover, at the promoter of WAKMAR2, we used PROMO software, version 3.0.2, to identify several putative binding sites of transcription factors known to interact with Smad complexes, for example, AP1, HNF-1B, HOXD9, and HOXD10, as well as nuclear receptors like the glucocorticoid receptors a and b, supporting our findings of TGF-beinduced WAKMAR2 expression (Farré et al, 2003;Messeguer et al, 2002). Of note, WAKMAR2 was recently reported to be downregulated in esophageal squamous cell carcinoma and gastric cardia adenocarcinoma due to aberrant hypermethylation of CpG islands (Guo et al, 2016a(Guo et al, , 2016b. We noticed that the potential binding sites of Smad3 and several aforementioned transcription factors, for example, AP-1, glucocorticoid receptor a/b, HOXD9, and HOXD10, co-localized with CpG islands at the WAKMAR2 = (d) Luciferase activity was measured in keratinocytes transfected with NF-kB reporter and Ctr or GapmeR1 for 24 hours and treated with TNF-a for 1 or 3 hours (n ¼ 4).…”

Section: Discussionsupporting

confidence: 83%

“…Recently, Tsoi et al (2015) profiled lncRNA expression in psoriasis skin, revealing LOC100130476 as top downregulated in lesional compared with nonlesional skin of psoriasis patients, which is a chronic inflammatory skin disease sharing some features with wounded skin, for example, epidermis thickening and inflammation (Morhenn et al, 2013;Nickoloff et al, 2006). Also, LOC100130476 was recently reported to be downregulated in esophageal squamous cell carcinoma (Guo et al, 2016a). Among the 53 human tissues characterized in the Genotype-Tissue Expression Project (Lonsdale et al, 2013), the skin has the highest LOC100130476 expression, suggesting its functional role in the skin.…”

Section: Introductionmentioning

confidence: 99%

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WAKMAR2, a Long Noncoding RNA Downregulated in Human Chronic Wounds, Modulates Keratinocyte Motility and Production of Inflammatory Chemokines

Herter

Toma

et al. 2019

Journal of Investigative Dermatology

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Chronic wounds represent a major and growing health and economic burden worldwide. A better understanding of molecular mechanisms of normal as well as impaired wound healing is needed to develop effective treatment. Herein we studied the potential role of long noncoding RNA LOC100130476 in skin wound repair. LOC100130476 is an RNA polymerase IIeencoded polyadenylated transcript present in both cytoplasm and nucleus. We found that its expression was lower in wound-edge keratinocytes of human chronic wounds compared to normal wounds of healthy donors and intact skin. In cultured keratinocytes, LOC100130476 expression was induced by TGF-b signaling. By reducing LOC100130476 expression with antisense oligos or activating its transcription with CRISPR/Cas9 Synergistic Activation Mediator system, we showed that LOC100130476 restricted the production of inflammatory chemokines by keratinocytes, while enhancing cell migration. In line with this, knockdown of LOC100130476 impaired re-epithelization of human ex vivo wounds. Based on these results, we named LOC100130476 wound and keratinocyte migrationeassociated long noncoding RNA 2 (WAKMAR2). Moreover, we identified a molecular network that may mediate the biological function of WAKMAR2 in keratinocytes using microarray. In summary, our data suggest that WAKMAR2 is an important regulator of skin wound healing and its deficiency may contribute to the pathogenesis of chronic wounds.Abbreviations: DFU, diabetic food ulcer; lncRNA, long noncoding RNA; QRT-PCR, quantitative real-time reverse transcriptase PCR; VU, venous ulcer; WAKMAR 2, wound and keratinocyte migrationeassociated long noncoding RNA 2

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

WAKMAR2, a Long Noncoding RNA Downregulated in Human Chronic Wounds, Modulates Keratinocyte Motility and Production of Inflammatory Chemokines

Herter

Toma

et al. 2019

Journal of Investigative Dermatology

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“…Another lincRNA induced in mouse macrophages after LPS stimulation is located at mouse chromosome 10 proximal to the tumor necrosis factor a-induced protein 3 (Tnfaip3) gene (27). An ortholog transcript in human is LOC100130476, located on 6q23.3 (GRCh38/hg38, from chr6:137823670 to 137868233, NR_049793.1) (28,29). The potential function of this lincRNA in regulation of inflammatory responses in macrophages is unclear.…”

mentioning

confidence: 99%

A long noncoding RNA, lincRNA‐Tnfaip3, acts as a coregulator of NF‐κB to modulate inflammatory gene transcription in mouse macrophages

Ming

Gong

et al. 2016

FASEB j.

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Long intergenic noncoding RNAs (lincRNAs) are long noncoding transcripts (>200 nt) from the intergenic regions of annotated protein-coding genes. We report here that the lincRNA gene , located at mouse chromosome 10 proximal to the tumor necrosis factor α-induced protein 3 () gene, is an early-primary response gene controlled by nuclear factor-κB (NF-κB) signaling in murine macrophages. Functionally, lincRNA- Tnfaip3 appears to mediate both the activation and repression of distinct classes of inflammatory genes in macrophages. Specifically, induction of lincRNA-Tnfaip3 is required for the transactivation of NF-κB-regulated inflammatory genes in response to bacterial LPSs stimulation. LincRNA-Tnfaip3 physically interacts with the high-mobility group box 1 (Hmgb1), assembling a NF-κB/Hmgb1/lincRNA-Tnfaip3 complex in macrophages after LPS stimulation. This resultant NF-κB/Hmgb1/lincRNA-Tnfaip3 complex can modulate Hmgb1-associated histone modifications and, ultimately, transactivation of inflammatory genes in mouse macrophages in response to microbial challenge. Therefore, our data indicate a new regulatory role of NF-κB-induced lincRNA-Tnfaip3 to act as a coactivator of NF-κB for the transcription of inflammatory genes in innate immune cells through modulation of epigenetic chromatin remodeling.-Ma, S., Ming, Z., Gong, A.-Y., Wang, Y., Chen, X., Hu, G., Zhou, R., Shibata, A., Swanson, P. C., Chen, X.-M. A long noncoding RNA, LincRNA-Tnfaip3, acts as a coregulator of NF-κB to modulate inflammatory gene transcription in mouse macrophages.

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“…CASC9 knockdown could significantly suppress cell migration and invasion, and increased CASC9 expression was associated with cell differentiation in vitro , indicating that CASC9 may be identified as a new promising biomarker for poor prognosis and a potential therapeutic target for treating esophageal cancer [36]. lncRNA LOC100130476 up-regulation could suppress cell proliferation and invasion, and hypermethylation of CpG sites in exon 1 could down-regulate LOC100130476 expression in esophageal cancer, which could predict the clinical TNM stage and pathological differentiation [37]. lncRNA H19 was significantly increased and correlated with tumor invasion depth and metastasis.…”

Section: Non-coding Rnas Molecular Functions In Esophageal Cancermentioning

confidence: 99%

“…Hypermethylation of CpG sites in the exon 1 and low expression of LOC100130476 could predict poor survival [37]. HOTAIR overexpression was correlated with short survival in esophageal cancer regardless of the ethnicities, indicating that high HOTAIR level may be a prognostic factor for esophageal cancer [53].…”

Section: Potential Biomarkers and Therapeutic Targets For Human Esophmentioning

confidence: 99%

Non-coding RNAs: new biomarkers and therapeutic targets for esophageal cancer

et al. 2017

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Esophageal cancer is one of the most common gastrointestinal malignant diseases and there is still no effective treatment. The incidence of esophageal cancer in the world is relatively high and on the increase year by year. Thus, the elaboration on the carcinogenesis of esophageal cancer and the identification of new biomarkers and therapeutic targets is quite beneficial to optimizing the current therapeutic regimen for treating such deadly disease. More and more evidence has shown that non-coding RNAs play an important role in the development and progression of multiple human cancers, including esophageal cancer. microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two functional kinds of non-coding RNAs that have been well investigated. They exert tumor suppressive or promoting effect by specifically regulating the expression of certain downstream target genes, which is tumor specific. It is also proved that miRNAs and lncRNAs level in tissue and plasma from esophageal cancer patients are closely correlated with the survival and disease progression, which could be used as a prognostic factor and therapeutic target for esophageal cancer.

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Aberrant methylation-mediated downregulation of long noncoding RNA LOC100130476 correlates with malignant progression of esophageal squamous cell carcinoma

Cited by 21 publications

References 34 publications

WAKMAR2, a Long Noncoding RNA Downregulated in Human Chronic Wounds, Modulates Keratinocyte Motility and Production of Inflammatory Chemokines

WAKMAR2, a Long Noncoding RNA Downregulated in Human Chronic Wounds, Modulates Keratinocyte Motility and Production of Inflammatory Chemokines

A long noncoding RNA, lincRNA‐Tnfaip3, acts as a coregulator of NF‐κB to modulate inflammatory gene transcription in mouse macrophages

Non-coding RNAs: new biomarkers and therapeutic targets for esophageal cancer

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