Differential Methylation of lncRNA
            <i>KCNQ1OT1</i>
            Promoter Polymorphism was Associated with Symptomatic Cardiac Long QT

Coto, Eliécer; Calvo, David; Reguero, Julián R.; Morı́s, César; Rubín, José M.; Díaz‐Corte, Carmen; Gil‐Peña, Helena; Alosno, Belén; Iglesias, Sara; Gómez, Juan

doi:10.2217/epi-2017-0024

Cited by 28 publications

(22 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have revealed that polymorphisms in the promoter region of GAS5 are associated with different types of cancers [30,31]. For example, Li et al [18] found that rs145204276 in the promoter region of GAS5 played a protective role in the development of gastric cancer through the regulation of GAS5.…”

Section: Discussionmentioning

confidence: 99%

Association between polymorphism in the promoter region of lncRNA GAS5 and the risk of colorectal cancer

Wang

Yang

et al. 2019

Bioscience Reports

View full text Add to dashboard Cite

The growth arrest special 5 (GAS5), as a research hotspot of long noncoding RNAs (lncRNAs), has been reported to be associated with colorectal cancer (CRC). However, the association between polymorphisms in GAS5 and the risk of CRC was not clear. In the present study, a case–control study in 1078 CRC patients and 1175 matched healthy controls was performed to evaluate the association between the potential functional genetic variants in GAS5 and the risk of CRC. PCR-TaqMan, qPCR, dual-luciferase assay, electrophoretic mobility shift assay (EMSA), flow cytometry, migration and invasion assays were performed to evaluate the function of polymorphism. Results showed that subjects carrying the rs55829688 CT/TT genotypes had a significantly higher risk of CRC when compared with the CC genotype. Further qPCR assay confirmed that the CRC tissues with rs55829688 CT/TT genotypes had a higher GAS5 mRNA expression level. The dual-luciferase assay, qPCR and EMSA assay revealed that rs55829688 T>C polymorphism could decrease the expression level of GAS5 by impacting the binding ability of the transcription factor Yin Yang-1 (YY1) to the GAS5 promoter region. The expression of apoptosis-related proteins were detected by Western blot. Further, flow cytometry, migration, and invasion experiments showed that GAS5 repressed apoptosis and increased invasion and migration capability of CRC cells. Taken together, our findings provided evidence that the rs55829688 variant in the GAS5 promoter was associated with the risk of CRC and decreased expression of GAS5 by affecting the binding affinity of the transcription factors YY1 to GAS5.

show abstract

Section: Discussionmentioning

confidence: 99%

Association between polymorphism in the promoter region of lncRNA GAS5 and the risk of colorectal cancer

Wang

Yang

et al. 2019

Bioscience Reports

View full text Add to dashboard Cite

show abstract

“…Sunamura et al showed that β-catenin promoted the development of colorectal cancer by directly up-regulating the transcription of KCNQ1OT1 [50]. Differential methylation of KCNQ1OT1 promoter polymorphism controlled its expression and associated with cardiac long QT [51]. Here we don't know the mechanism responsible for KCNQ1OT1 up-regulation, which should be explored further in future studies.…”

Section: Discussionmentioning

confidence: 81%

LncRNA KCNQ1OT1 sponges miR-15a to promote immune evasion and malignant progression of prostate cancer via up-regulating PD-L1

Chen

Liu

et al. 2020

Cancer Cell Int

View full text Add to dashboard Cite

Background: We focused on the KCNQ1OT1/miR-15a/PD-L1 axis and explored its significance in regulating immune evasion and malignant behaviors of prostate cancer (PC) cells. Methods: The expression levels of KCNQ1OT1, miR-15a, PD-L1, and CD8 in cells or tissues were examined by RT-qPCR, western blot or immunohistochemistry (IHC) assays. The direct regulations between KCNQ1OT1, miR-15a and PD-L1 were validated by luciferase reporter assay. PC cells were co-cultured with CD8 + T cells to study the immune evasion. Proliferation, apoptosis, migration and invasion abilities were detected by MTT, flow cytometry, wound healing and Transwell assays, respectively. The cytotoxicity of CD8 + T cells was determined by LDH cytotoxicity Kit. Epithelial-mesenchymal transition (EMT) and Ras/ERK signaling markers were evaluated by western blot. Results: KCNQ1OT1, PD-L1 and CD8 were increased, while miR-15a was decreased in PC tissues. MiR-15a directly bound to the 3′-UTR of PD-L1 and inhibited the expression of PD-L1. Overexpressing miR-15a in PC cells was sufficient to promote cytotoxicity and proliferation, while inhibit apoptosis of CD8 + T cells, and also suppressed viability, migration, invasion and EMT while promoted apoptosis of PC cells. The above anti-tumor effects of miR-15a were reversed by overexpressing PD-L1. KCNQ1OT1 sponged miR-15a and released its inhibition on PD-L1. Functionally, KCNQ1OT1 in PC cells was essential for suppressing the cytotoxicity of CD8 + T cells and maintaining multiple malignant phenotypes of PC cells. The Ras/ERK signaling was suppressed after overexpressing miR-15a or knocking down KCNQ1OT1. Conclusions: LncRNA KCNQ1OT1 sponges miR-15a to promote immune evasion and malignant progression of PC via up-regulating PD-L1.

show abstract

“…In the mouse, for example, the lncRNA Kcnq1ot1 can regulate the expression of Kcnq1 43 . KCNQ1OT1 is expressed in humans, and polymorphisms in the KCNQ1OT1 promoter are associated with prolonged QT intervals 44 . Although limited, transcriptional profiling of lncRNAs in the human heart has also identified several lncRNAs associated with cardiovascular disease(s) 12 – 15 .…”

Section: Discussionmentioning

confidence: 99%

Regional Differences in mRNA and lncRNA Expression Profiles in Non-Failing Human Atria and Ventricles

Johnson

Matkovich

Nerbonne

2018

Sci Rep

View full text Add to dashboard Cite

The four chambers of the human heart play distinct roles in the maintenance of normal cardiac function, and are differentially affected by inherited/acquired cardiovascular disease. To probe the molecular determinants of these functional differences, we examined mRNA and lncRNA expression profiles in the left (LA) and right (RA) atria, the left (LV) and right (RV) ventricles, and the interventricular septum (IVS) of non-failing human hearts (N = 8). Analysis of paired atrial and ventricular samples (n = 40) identified 5,747 mRNAs and 2,794 lncRNAs that were differentially (>1.5 fold; FDR < 0.05) expressed. The largest differences were observed in comparisons between the atrial (RA/LA) and ventricular (RV/LV/IVS) samples. In every case (e.g., LA vs LV, LA vs RV, etc.), >2,300 mRNAs and >1,200 lncRNAs, corresponding to 17–28% of the total transcripts, were differentially expressed. Heterogeneities in mRNA/lncRNA expression profiles in the LA and RA, as well as in the LV, RV and IVS, were also revealed, although the numbers of differentially expressed transcripts were substantially smaller. Gender differences in mRNA and lncRNA expression profiles were also evident in non-failing human atria and ventricles. Gene ontology classification of differentially expressed gene sets revealed chamber-specific enrichment of numerous signaling pathways.

show abstract

Differential Methylation of lncRNA KCNQ1OT1 Promoter Polymorphism was Associated with Symptomatic Cardiac Long QT

Abstract: Our findings supported a role for the differential methylation/imprinting of KCNQ1OT1 in the risk for symptomatic prolonged QTc.

Cited by 28 publications

References 31 publications

Association between polymorphism in the promoter region of lncRNA GAS5 and the risk of colorectal cancer

Association between polymorphism in the promoter region of lncRNA GAS5 and the risk of colorectal cancer

LncRNA KCNQ1OT1 sponges miR-15a to promote immune evasion and malignant progression of prostate cancer via up-regulating PD-L1

Regional Differences in mRNA and lncRNA Expression Profiles in Non-Failing Human Atria and Ventricles

Contact Info

Product

Resources

About