Methylation-mediated silencing of the LIM homeobox 6 (LHX6) gene promotes cell proliferation in human pancreatic cancer

Abudurexiti, Yakefujiang; Gu, Zhaodi; Chakma, Kanchan; Hata, Tatsuo; Motoi, Fuyuhiko; Unno, Michiaki; Horii, Akira; Fukushige, Shinichi

doi:10.1016/j.bbrc.2020.03.120

Cited by 9 publications

(11 citation statements)

References 22 publications

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“…An increasing number of studies have confirmed that epigenetic alterations can mediate the effects of environmental factors on disease ( Agache et al, 2020 ). As the most typical epigenetic alteration, DNA hypermethylation is closely linked to improper transcriptional silencing and the functional loss of genes to accelerate the growth of tumor cells and promote tumorigenesis and development ( Abudurexiti et al, 2020 ). To screen for early-stage tumors, methylation-based biomarkers detected from tissue samples were highlighted in the recent long-term study ( Ibrahim et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Association between EPHA5 methylation status in peripheral blood leukocytes and the risk and prognosis of gastric cancer

Han¹,

Li²,

Zhai³

et al. 2022

PeerJ

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Purpose Altered DNA methylation, genetic alterations, and environmental factors are involved in tumorigenesis. As a tumor suppressor gene, abnormal EPHA5 methylation was found in gastric cancer (GC) tissues and was linked to the initiation, progression and prognosis of GC. In this study, the EPHA5 methylation level in peripheral blood leukocytes (PBLs) was detected to explore its relationship with GC risk and prognosis. Methods A total of 366 GC cases and 374 controls were selected as the subjects of this study to collect their environmental factors, and the EPHA5 methylation status was detected through the methylation-sensitive high-resolution melting method. Logistic regression analysis was utilized to evaluate the associations among EPHA5 methylation, environmental factors and GC risk. Meanwhile, the propensity score (PS) was used to adjust the imbalance of some independent variables. Results After PS adjustment, EPHA5 Pm (positive methylation) was more likely to increase the GC risk than EPHA5 Nm (negative methylation) (ORb = 1.827, 95% CI [1.202–2.777], P = 0.005). EPHA5 Pm had a more significant association with GC risk in the elderly (ORa = 2.785, 95% CI [1.563–4.961], P = 0.001) and H. pylori-negative groups (ORa = 2.758, 95% CI [1.369–5.555], P = 0.005). Moreover, the combined effects of EPHA5 Pm and H. pylori infection (ORca = 3.543, 95% CI [2.233–5.621], P < 0.001), consumption of alcohol (ORca = 2.893, 95% CI [1.844–4.539], P < 0.001), and salty food intake (ORca = 4.018, 95% CI [2.538–6.362], P < 0.001) on increasing the GC risk were observed. In addition, no convincing association was found between EPHA5 Pm and the GC prognosis. Conclusions EPHA5 methylation in PBLs and its combined effects with environmental risk factors are related to the GC risk.

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Section: Discussionmentioning

confidence: 99%

Association between EPHA5 methylation status in peripheral blood leukocytes and the risk and prognosis of gastric cancer

Han¹,

Li²,

Zhai³

et al. 2022

PeerJ

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“…The NPTX2 gene has been reported to inhibit proliferation and invasion in PDAC, 32 and three neurofilament genes, NEFL , NEFM , and NEFH , are methylated in many kinds of cancers, including PDAC, and are associated with an aggressive phenotype of breast cancer 33 . The LHX6 gene is also hypermethylated in cervical, 34 lung, 35 breast, 36 and pancreatic 37 cancers; its forced expression suppressed tumorigenic phenotypes such as cell proliferation, migration, and invasion in these cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic inactivation of IRX4 is responsible for acceleration of cell growth in human pancreatic cancer

Chakma

Abudurexiti

et al. 2020

Cancer Science

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Epigenetic gene silencing by aberrant DNA methylation is one of the important mechanisms leading to loss of key cellular pathways in tumorigenesis. Methyl‐CpG‐targeted transcriptional activation (MeTA) reactivates hypermethylation‐mediated silenced genes in a different way from DNA‐demethylating agents. Microarray coupled with MeTA (MeTA‐array) identified seven commonly hypermethylation‐mediated silenced genes in 12 pancreatic ductal adenocarcinoma (PDAC) cell lines. Among these, we focused on IRX4 (Iroquois homeobox 4) because IRX4 is located at chromosome 5p15.33 where PDAC susceptibility loci have been identified through genome‐wide association study. IRX4 was greatly downregulated in all of the analyzed 12 PDAC cell lines by promoter hypermethylation. In addition, the IRX4 promoter region was found to be frequently and specifically hypermethylated in primary resected PDACs (18/28: 64%). Reexpression of IRX4 inhibited colony formation and proliferation in two PDAC cell lines, PK‐1 and PK‐9. In contrast, knockdown of IRX4 accelerated cell proliferation in an IRX4‐expressing normal pancreatic ductal epithelial cell line, HPDE‐1. Because IRX4 is a sequence‐specific transcription factor, downstream molecules of IRX4 were pursued by microarray analyses utilizing tetracycline‐mediated IRX4 inducible PK‐1 and PK‐9 cells; CRYAB, CD69, and IL32 were identified as IRX4 downstream candidate genes. Forced expression of these genes suppressed colony formation abilities for both PK‐1 and PK‐9. These results suggest that DNA methylation‐mediated silencing of IRX4 contributes to pancreatic tumorigenesis through aberrant transcriptional regulation of several cancer‐related genes.

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“…Recent study indicated that DNA hypermethylation undergoes further progression after colorectal cancer cell migrating into liver due to the fact that there is no change of DNA hypermethylation between primary colorectal cancer and colorectal cancer liver metastasis [15]. In addition, the hypermethylation of LHX6 could promote the proliferation of human pancreatic cancer [16]. The CpG island hypermethylation could inhibit the expression level of BARX2 resulting in the inhibition of proliferation and invasion of gastric cancer cells [17].…”

Section: Discussionmentioning

confidence: 99%

Identification of Differential Methylation Regions and Correspondence Targeted Genes in Oral Squamous Cell Carcinoma

Niu¹,

Shan²,

Guo³

2020

Preprint

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Background The differential methylation included hypermethylation and hypomethylation plays significant role in the progression of many kind of cancers but study little in oral squamous cell carcinoma (OSCC). Methods GSE123781 and GSE87053 was used to analysis the differential methylation regions (DMRs) and predict the target genes in OSCC by R software and wANNOVAR respectively. the biological process and cell pathways of common targeted genes between GSE123781 and GSE87053 were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analysis. The hub genes (hub genes 1) in common targeted genes associated with cancer biological process was identified by protein to protein interaction network (PPI). In addition, GSE74530 and GSE30784 was used to identify common differentially expressed genes (DEGs) in OSCC by R software. The biological process and cell pathways of common DEGs was analyzed by GO and KEGG enrichment analysis. The hub genes (hub genes 2) in common DEGs associated with cancer biological process was identified by PPI network. The significant hub genes between hub genes 1 and hub genes 2 were identified by Venn picture. Finally, the expression level of significant hub genes and correspondence relationship with head and neck squamous cell carcinoma (HNSCC) patient survival were confirmed by The Cancer Genome Atlas (TCGA) dataset. Results There are 2146 common targeted genes regulated by DMRs between GSE123781 and GSE87053 and 278 hub genes in common targeted genes associated with cancer biological process. In addition, there are 895 common DEGs between GSE74530 and GSE30784 and 144 hub genes in common DEGs associated with cancer biological process. There are 9 significant hub genes between hub genes 1 and hub genes 2. Finally, these 9 significant hub genes differentially expressed in HNSCC tissues except CCR7 and quite associated with the survival of HNSCC patients. Conclusions CCR7, ETS1, RUNX3, CCR1, C3AR1, LAMB1, IRF7, LGALS3 and CDKN3 both are DEGs and regulated by DMRs in OSCC, which are quite associated with the progression of OSCC and the survival of HNSCC patients. All of these genes have much potential to be new biomarkers in targeted therapy of OSCC.

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Methylation-mediated silencing of the LIM homeobox 6 (LHX6) gene promotes cell proliferation in human pancreatic cancer

Cited by 9 publications

References 22 publications

Association between EPHA5 methylation status in peripheral blood leukocytes and the risk and prognosis of gastric cancer

Association between EPHA5 methylation status in peripheral blood leukocytes and the risk and prognosis of gastric cancer

Epigenetic inactivation of IRX4 is responsible for acceleration of cell growth in human pancreatic cancer

Identification of Differential Methylation Regions and Correspondence Targeted Genes in Oral Squamous Cell Carcinoma

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