Hs.137007 is a novel epigenetic marker hypermethylated and up-regulated in breast cancer

Kim, Tae Woo; Kim, Yoo Jung; Lee, Hyunji; Min, Sun Young; Kang, Hyejin; Kim, Sun Jung

doi:10.3892/ijo_00000592

Cited by 16 publications

(21 citation statements)

References 30 publications

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“…In endometrial cancer, survivin promoter hypermethylation of CpG within transcriptional repressor binding sites was correlated with its upregulation [56]. In the same way, in breast cancer samples, the promoter of the KLHDC7B gene was hypermethylated and associated with its overexpression in comparison with normal mammary tissue [57]. In vitro , the methylation of the human glycoprotein hormone α-subunit ( GPHα ) gene was found to be hypermethylated in cell lines producing high amount of this protein, whereas low level were detected in cell lines with hypomethylated GPHα gene sequence [58].…”

Section: Discussionmentioning

confidence: 83%

Aberrant Promoter Methylation and Expression of UTF1 during Cervical Carcinogenesis

Guenin

Mouallif

Deplus³

et al. 2012

PLoS ONE

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Promoter methylation profiles are proposed as potential prognosis and/or diagnosis biomarkers in cervical cancer. Up to now, little is known about the promoter methylation profile and expression pattern of stem cell (SC) markers during tumor development. In this study, we were interested to identify SC genes methylation profiles during cervical carcinogenesis. A genome-wide promoter methylation screening revealed a strong hypermethylation of Undifferentiated cell Transcription Factor 1 (UTF1) promoter in cervical cancer in comparison with normal ectocervix. By direct bisulfite pyrosequencing of DNA isolated from liquid-based cytological samples, we showed that UTF1 promoter methylation increases with lesion severity, the highest level of methylation being found in carcinoma. This hypermethylation was associated with increased UTF1 mRNA and protein expression. By using quantitative RT-PCR and Western Blot, we showed that both UTF1 mRNA and protein are present in epithelial cancer cell lines, even in the absence of its two main described regulators Oct4A and Sox2. Moreover, by immunofluorescence, we confirmed the nuclear localisation of UTF1 in cell lines. Surprisingly, direct bisulfite pyrosequencing revealed that the inhibition of DNA methyltransferase by 5-aza-2′-deoxycytidine was associated with decreased UTF1 gene methylation and expression in two cervical cancer cell lines of the four tested. These findings strongly suggest that UTF1 promoter methylation profile might be a useful biomarker for cervical cancer diagnosis and raise the questions of its role during epithelial carcinogenesis and of the mechanisms regulating its expression.

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Section: Discussionmentioning

confidence: 83%

Aberrant Promoter Methylation and Expression of UTF1 during Cervical Carcinogenesis

Guenin

Mouallif

Deplus³

et al. 2012

PLoS ONE

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“…Alterations in this protein superfamily have been associated with various types of cancer, including leukemia, lung, prostate, brain, and Hodgkin's disease (Gupta and Beggs, ). To the best of our knowledge, the only report that associates this gene with breast cancer, reported the hypermethylation and over‐regulation of this gene in mammary tumors, suggesting a possible role as an epigenetic marker (Kim et al ., ). However, the role of its non‐coding antisense LncKLHDC7B was unknown.…”

Section: Discussionmentioning

confidence: 98%

Expression of long non‐coding RNA ENSG00000226738 (LncKLHDC7B) is enriched in the immunomodulatory triple‐negative breast cancer subtype and its alteration promotes cell migration, invasion, and resistance to cell death

et al. 2019

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Triple negative breast cancer ( TNBC ) represents an aggressive phenotype with poor prognosis compared with ER , PR, and HER 2‐positive tumors. TNBC is a heterogeneous disease, and gene expression analysis has identified seven molecular subtypes. Accumulating evidence demonstrates that long non‐coding RNA (lnc RNA ) are involved in regulation of gene expression and cancer biology, contributing to essential cancer cell functions. In this study, we analyzed the expression profile of lnc RNA in TNBC subtypes from 156 TNBC samples, and then characterized the functional role of Lnc KLHDC 7B ( ENSG 00000226738 ). A total of 710 lnc RNA were found to be differentially expressed between TNBC subtypes, and a subset of these altered lnc RNA were independently validated. We discovered that Lnc KLHDC 7B ( ENSG 00000226738 ) acts as a transcriptional modulator of its neighboring coding gene KLHDC 7B in the immunomodulatory subtype. Furthermore, Lnc KLHDC 7B knockdown enhanced migration and invasion, and promoted resistance to cellular death. Our findings confirmed the contribution of Lnc KLHDC 7B to induction of apoptosis and inhibition of cell migration and invasion, suggesting that TNBC tumors with enrichment of Lnc KLHDC 7B may exhibit distinct regulatory activity, or that this may be a generalized process in breast cancer. Additionally, in silico analysis confirmed for the first time that the low expression of KLHDC 7B and Lnc KLHDC 7B is associated with poor prognosis in patients with breast cancer.

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“…Has been shown to be up-regulated in breast cancer tissues [18] KRT81 Expressed in breast carcinomas [19] GPBP1 Plays a role in the development of atherosclerosis [20] THSD4 Plays a role in connective tissue formation [21] C4orf36…”

Section: Vgll4mentioning

confidence: 99%

Use of Next Generation Sequencing in the Identification of Long Non-Coding RNAs as Potential Players in Breast Cancer Prevention

Santucci-Pereira

Barton²,

Russo³

et al. 2013

Transcriptomics

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Hs.137007 is a novel epigenetic marker hypermethylated and up-regulated in breast cancer

Cited by 16 publications

References 30 publications

Aberrant Promoter Methylation and Expression of UTF1 during Cervical Carcinogenesis

Aberrant Promoter Methylation and Expression of UTF1 during Cervical Carcinogenesis

Expression of long non‐coding RNA ENSG00000226738 (LncKLHDC7B) is enriched in the immunomodulatory triple‐negative breast cancer subtype and its alteration promotes cell migration, invasion, and resistance to cell death

Use of Next Generation Sequencing in the Identification of Long Non-Coding RNAs as Potential Players in Breast Cancer Prevention

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