Loss of LDOC1 Expression by Promoter Methylation in Cervical Cancer Cells

Buchholtz, Marie-Luise; Jückstöck, Julia; Weber, Elena; Mylonas, Ioannis; Dian, Darius; Brüning, Ansgar

doi:10.3109/07357907.2013.845671

Cited by 19 publications

(22 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4 These data suggest the possibility that the increased expression of GNL3L, particularly in gastric cancer, may be due to the absence of inhibitory activity of LDOC1 owing to promoter hyper-methylation. 22,30 Furthermore, analysis of in vivo expression pattern of GNL3L and LDOC1 in various primary cancers from BioXpress database indicates an inverse correlation (Fig. 11), supporting the notion that the interplay between GNL3L and LDOC1 may be critical for cell growth control.…”

Section: Discussionmentioning

confidence: 77%

“…In addition, we have characterized Leucine Zipper Downregulated in Cancer-1 (LDOC1) as a novel interacting partner of GNL3L that can modulate the stimulatory effect exerted on NF-kB by GNL3L. LDOC1 is a 17-kDa protein that is down-regulated in most pancreatic, gastric and cervical cancer cell lines 21,22 and is a negative regulator of NFkB. 23 The present investigation provides evidence that LDOC1-mediated GNL3L destabilization leads to decreased total cellular p65 pool, which in-turn results in reduced cell proliferation and apoptosis.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Leucine Zipper Down-regulated in Cancer-1 (LDOC1) interacts with Guanine nucleotide binding protein-like 3-like (GNL3L) to modulate Nuclear Factor-kappa B (NF-κB) signaling during cell proliferation

et al. 2016

View full text Add to dashboard Cite

Guanine nucleotide binding protein-like 3-like (GNL3L) is an evolutionarily conserved putative nucleolar GTPase belonging to the HSR1-MMR1 family. In the present study, using protein-protein interaction assays, we show that Leucine Zipper Down-regulated in Cancer-1 (LDOC1) is a novel interacting partner of GNL3L. Furthermore, our results reveal that ectopic expression of LDOC1 destabilizes endogenous GNL3L levels and down modulates GNL3L-induced cell proliferation, in contrast, the knockdown of LDOC1 potentiates cell proliferation upon GNL3L expression. Interestingly, GNL3L upregulates NF-kB dependent transcriptional activity by modulating the expression of NF-kB subunit p65, which is reversed upon coexpression of LDOC1 with GNL3L. GNL3L also potentiates TNF-a mediated NF-kB activity. In addition, antiapoptotic function of GNL3L is impaired upon p65 knockdown, suggesting its critical role in GNL3L mediated cell proliferation/survival. An inverse correlation of GNL3L and LDOC1 expression profiles in various tumor tissues from BioXpress database indicate their critical role in cancer. Collectively, our data provides evidence that GNL3L-LDOC1 interplay regulates cell proliferation through the modulation of NFkB pathway during tumorigenesis.

show abstract

Section: Discussionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Leucine Zipper Down-regulated in Cancer-1 (LDOC1) interacts with Guanine nucleotide binding protein-like 3-like (GNL3L) to modulate Nuclear Factor-kappa B (NF-κB) signaling during cell proliferation

et al. 2016

View full text Add to dashboard Cite

show abstract

“…The RNA-seq analysis revealed that SB induced the expression of several tumor suppressor genes were repressed due to hypermethylation or Loss of Heterozygosity (LOH) as indicated in Table 3. The X-chromosome methylation pattern also has been affected as indicated by the increased LDOC1 expression, a gene whose promoter known to be hypermethylated in cancer [54]. However, a detailed methylation-specific sequencing and analysis needs to be carried out to further gain a deeper insight onto differential methylation effects of SB.…”

Section: Discussionmentioning

confidence: 99%

Differential effects of two HDAC inhibitors with distinct concomitant DNA hypermethylation or hypomethylation in breast cancer cells

Kalle

Wang

2019

Preprint

View full text Add to dashboard Cite

DNA methylation and histone acetylation are the two important epigenetic phenomena that control the status of X-chromosome inactivation (XCI), a process of dosage compensation in mammals resulting in active X chromosome (Xa) and inactive X chromosome (Xi) in females.While DNA methyltransferases (DNMTs) are known to maintain the DNA hypermethylation of Xi, it remains to be determined how one or a few of 18 known histone deacetylases (HDACs) contribute(s) to Xi maintenance. Herein we found that HDAC1/2/4/6 were overexpressed in breast cancer cells, MDA-MB-231, with Xa/Xa status compared to normal breast epithelial cells, MCF10A, with Xa/Xi status. Inhibition of these overexpressed HDACs with two different drugs, sodium butyrate (SB) and Trichostatin A (TSA), caused surprisingly distinct effects on global DNA methylation: hypermethylation and hypomethylation, respectively, as well as distinct effects on a repressing histone mark H3K27me3 for heterochromatin and an active mark H3K56ac for DNA damage. Surveying three DNMTs through immunoblot analyses for insights revealed the up-or down-regulation of DNMT3A upon drug treatments in a concentration-dependent manner. These results correlated with the decreased XIST and increased TSIX expression in MDA-MB 231 as a possible mechanism of Xi loss and were reversed with SB treatment. Further RNA-seq analysis indicated differential gene expression correlating with the promoter methylation status of a few genes. Collectively, our results demonstrate a crosstalk between HDACs and DNMTs and the novel involvement of HDACs in skewed Xi in breast cancer.

show abstract

“…15 Therefore, LDOC1 is a potential biomarker and putative therapeutic target for osteosarcoma. Consistent with its role as a tumor suppressor gene, decreased expression of LDOC1 has been shown in several other types of cancers, including prostate cancer, 16 cervical cancer, 17 ovarian cancer, 18 oral squamous cell carcinoma, 19 and thyroid cancer. 13 LDOC1 has been reported to be involved in regulation of proliferation and apoptosisin cancer.…”

Section: Introductionmentioning

confidence: 78%

LDOC1 regulates Wnt5a expression and osteosarcoma cell metastasis and is correlated with the survival of osteosarcoma patients

Yong

Xie

et al. 2017

Tumour Biol.

View full text Add to dashboard Cite

Osteosarcomas are common bone malignancies in children and adolescents. LDOC1 (leucine zipper, down-regulated in cancer 1), a tumor suppressor, is down-regulated in many cancers. In this study, we investigated the role of LDOC1 in tumor metastasis and its prognostic significance in osteosarcomas. We established osteosarcoma cells stably expressing LDOC1, driven by an HIV-based lentiviral system. We investigated the impact of LDOC1 on migration and invasion abilities in these cells using a transwell assay. LDOC1-associated changes in expression of metastasis-promoting genes were analyzed with a quantitative real-time polymerase chain reaction primer array. A xenograft tumor model (n = 7 mice/group) was used to assess the effect of LDOC1 on osteosarcoma metastasis in vivo. The overall survival and disease-free survival of osteosarcoma patients (n = 74) were analyzed retrospectively based on immunohistochemical analysis of LDOC1 levels in tumors and Kaplan–Meier analysis. LDOC1-expressing osteosarcoma cells displayed decreased migration and invasion in vitro. The quantitative real-time polymerase chain reaction primer array data showed that increased LDOC1 expression up-regulated many metastasis-suppressor genes. In the xenograft model, micro-computed tomography imaging data indicated that increased LDOC1 expression is associated with weaker lung metastasis ability. The Wnt5a signaling pathway promotes osteosarcoma metastasis; LDOC1 expression decreased Wnt5a levels in osteosarcoma cells. Kaplan–Meier analysis showed that higher LDOC1 expression was associated with improved osteosarcoma patient overall survival and disease free survival (p = 0.022). Our data show that LDOC1 is a tumor suppressor in osteosarcoma, and that it regulates metastasis of osteosarcoma cells. Furthermore, LDOC1 might be a valuable prognostic marker in osteosarcomas.

show abstract

Loss of LDOC1 Expression by Promoter Methylation in Cervical Cancer Cells

Cited by 19 publications

References 25 publications

Leucine Zipper Down-regulated in Cancer-1 (LDOC1) interacts with Guanine nucleotide binding protein-like 3-like (GNL3L) to modulate Nuclear Factor-kappa B (NF-κB) signaling during cell proliferation

Leucine Zipper Down-regulated in Cancer-1 (LDOC1) interacts with Guanine nucleotide binding protein-like 3-like (GNL3L) to modulate Nuclear Factor-kappa B (NF-κB) signaling during cell proliferation

Differential effects of two HDAC inhibitors with distinct concomitant DNA hypermethylation or hypomethylation in breast cancer cells

LDOC1 regulates Wnt5a expression and osteosarcoma cell metastasis and is correlated with the survival of osteosarcoma patients

Contact Info

Product

Resources

About