Where long noncoding RNAs meet DNA methylation

Lai, Fang; Shiekhattar, Ramin

doi:10.1038/cr.2014.13

Cited by 36 publications

(34 citation statements)

References 13 publications

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“…Recently, increasing evidence confirmed that lncRNA can regulate DNA methylation of protein‐coding genes during the development of disease, and several studies reported that EPHB4 expression is activated by demethylation of the EPHB4 CpG island in the development of a variety of cancers . Interestingly, using BSP assays, we observed a robust increase in levels of DNA methylation of EPHB4 following depletion of BC005927.…”

Section: Discussionsupporting

confidence: 54%

Long noncoding RNA BC005927 upregulates EPHB4 and promotes gastric cancer metastasis under hypoxia

et al. 2018

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Hypoxia plays a critical role in the metastasis of gastric cancer (GC), yet the underlying mechanism remains largely unclear. It is also not known whether long, noncoding RNAs (lncRNAs) are involved in the contribution of hypoxia to GC metastasis. In the present study, we found that lncRNA BC005927 can be induced by hypoxia in GC cells and mediates hypoxia‐induced GC cell metastasis. Furthermore, BC005927 is frequently upregulated in GC samples and increased BC005927 expression was correlated with a higher tumor‐node‐metastasis stage. GC patients with higher BC005927 expression had poorer prognoses than those with lower expression. Additional experiments showed that BC005927 expression is induced by hypoxia inducible factor‐1 alpha (HIF‐1α); ChIP assay and luciferase reporter assays confirmed that this lncRNA is a direct transcriptional target of HIF‐1α. Next, we found that EPHB4, a metastasis‐related gene, is regulated by BC005927 and that the expression of EPHB4 was positively correlated with that of BC005927 in the clinical GC samples assessed. Intriguingly, EPHB4 expression was also increased under hypoxia, and its upregulation by BC005927 resulted in hypoxia‐induced GC cell metastasis. These results advance the current understanding of the role of BC005927 in the regulation of hypoxia signaling and offer new avenues for the development of therapeutic interventions against cancer progression.

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Section: Discussionsupporting

confidence: 54%

Long noncoding RNA BC005927 upregulates EPHB4 and promotes gastric cancer metastasis under hypoxia

et al. 2018

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“…23 A previously conducted functional study asserted that the methylation in CpG island of promoters results in silencing of its downstream genes at a transcriptional level, or the inactivation of tumour suppressor genes in specific cancers. However, lncRNA TNRC6C-AS1 could be enriched by DNMT1, DNMT2 and DNMT3 and might regulate STK4 methylation level through binding to CpG island of STK4 promoter.…”

Section: Silencing Of Tnrc6c-as1 Inhibited Tumorigenesis In Nude Micementioning

confidence: 99%

Suppression of long non‐coding RNA TNRC6C‐AS1 protects against thyroid carcinoma through DNA demethylation of STK4 via the Hippo signalling pathway

Yang

Guo

et al. 2019

Cell Proliferation

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Objectives: Thyroid carcinoma (TC) represents a malignant neoplasm affecting the thyroid. Current treatment strategies include the removal of part of the thyroid; however, this approach is associated with a significant risk of developing hypothyroidism.In order to adequately understand the expression profiles of TNRC6C-AS1 and STK4and their potential functions in TC, an investigation into their involvement with Hippo signalling pathway and the mechanism by which they influence TC apoptosis and autophagy were conducted.Methods: A microarray analysis was performed to screen differentially expressed lncRNAs associated with TC. TC cells were employed to evaluate the role of TNRC6C-AS1 by over-expression or silencing means. The interaction of TNRC6C-AS1 with methylation of STK4 promoter was evaluated to elucidate its ability to elicit autophagy, proliferation and apoptosis.Results: TNRC6C-AS1 was up-regulated while STK4 was down-regulated, where methylation level was elevated. STK4 was verified as a target gene of TNRC6C-AS1, which was enriched by methyltransferase. Methyltransferase's binding to STK4 increased expression of its promoter. Over-expressed TNRC6C-AS1 inhibited STK4 by promoting STK4 methylation and reducing the total protein levels of MST1 and LATS1/2. The phosphorylation of YAP1 phosphorylation was decreased, which resulted in the promotion of SW579 cell proliferation and tumorigenicity.Conclusion: Based on our observations, we subsequently confirmed the anti-proliferative, pro-apoptotic and pro-autophagy capabilities of TNRC6C-AS1 through STK4 methylation via the Hippo signalling pathway in TC.

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“…The lncRNA extra coding CCAAT enhancer binding protein alpha (ecCEBPA) is upregulated in gastric cancer cells [106]. The lncRNA ecCEBPA regulates DNA methylation at the CEBPA gene locus due to the interaction of ecCEBPA with DNA methyltransferase 1(DNMT1) [107,108]. The lncRNAs Xist and HOTAIR interact with the proteins polycomb repressive complex 2 (PRC2) and lysine-specific demethylase 1 (LSD1) to prevent the transcription of target genes, such as HDAC3 and E-cadherin, and regulate cancer metastasis [109,112,113].…”

Section: Epigenetics and Related Lncrnasmentioning

confidence: 99%

Long non-coding RNAs regulate drug resistance in cancer

et al. 2020

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Chemoresistance, whether intrinsic or acquired, is a major obstacle in the treatment of cancer. The resistance of cancer cells to chemotherapeutic drugs can result from various mechanisms. Over the last decade, it has been reported that 1ong noncoding RNAs (lncRNAs) can mediate carcinogenesis and drug resistance/sensitivity in cancer cells. This article reviews, in detail, recent studies regarding the roles of lncRNAs in mediating drug resistance.

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Where long noncoding RNAs meet DNA methylation

Cited by 36 publications

References 13 publications

Long noncoding RNA BC005927 upregulates EPHB4 and promotes gastric cancer metastasis under hypoxia

Long noncoding RNA BC005927 upregulates EPHB4 and promotes gastric cancer metastasis under hypoxia

Suppression of long non‐coding RNA TNRC6C‐AS1 protects against thyroid carcinoma through DNA demethylation of STK4 via the Hippo signalling pathway

Long non-coding RNAs regulate drug resistance in cancer

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