Alteration in the expression of MGMT and RUNX3 due to non-CpG promoter methylation and their correlation with different risk factors in esophageal cancer patients

Saikia, Snigdha; Rehman, Asad Ur; Barooah, Prajjalendra; Sarmah, Preeti; Bhattacharyya, Mallika; Deka, Muktanjalee; Deka, Manab; Goswami, Bhabadev; Husain, Syed Akhtar; Medhi, Subhash

doi:10.1177/1010428317701630

Cited by 8 publications

(5 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The gene expression level of Runx3 is controlled by promoters that are rich in CpG islands. Previous studies have reported that methylation of promoter regions results in silencing of Runx3 gene expression, which leads to the development of several diseases (49)(50)(51). The present study showed that the protein and mRNA levels of Runx3 were significantly decreased in the PM2.5 and OVA exposure groups.…”

Section: Discussionsupporting

confidence: 62%

Fine particulate matter induces airway inflammation by disturbing the balance between Th1/Th2 and regulation of GATA3 and Runx3 expression in BALB/c mice

Pang

Liu

et al. 2021

Mol Med Rep

View full text Add to dashboard Cite

The present study aimed to examine the effects of 2.5 µm particulate matter (PM2.5) on airway inflammation and to investigate the possible underlying mechanism. Specifically, the focus was on the imbalance of T helper (Th)1/Th2 cells and the dysregulated expression of transcription factors, including trans-acting T cell-specific transcription factor 3 (GATA3), runt-related transcription factor 3 (Runx3) and T-box transcription factor TBX21 (T-bet). In this study, ambient PM2.5 was collected and analyzed, male BALB/c mice were sensitized and treated with PBS, ovalbumin (OVA), PM2.5 or OVA + PM2.5. The effects of PM2.5 alone or PM2.5 + OVA on immunopathological changes, the expression of transcription factors GATA3, Runx3 and T-bet, and the imbalance of Th1/Th2 were investigated. It was found that PM2.5 + OVA co-exposure significantly enhanced inflammatory cell infiltration, increased higher tracheal secretions in lung tissue and upregulated respiratory resistance response to acetylcholine compared with PM2.5 or OVA single exposure and control groups. In addition, higher protein and mRNA expression levels of Th2 inflammatory mediators interleukin (IL)-4, IL-5 and IL-13 in bronchoalveolar lavage fluid were observed in PM2.5 + OVA treated mice, whereas the expression levels of GATA3 and STAT6 were exhibited in mice exposed to OVA + PM2.5 compared with the OVA and PM2.5 groups. By contrast, PM2.5 exposure decreased the protein and mRNA expression levels of Th1 cytokine interferon-γ and transcription factors Runx3 and T-bet, especially among asthmatic mice, different from OVA group, PM2.5 exposure only failed to influence the expression of T-bet. To conclude, PM2.5 exposure evoked the allergic airway inflammation response, especially in the asthmatic mouse model and led to Th1/Th2 imbalance. These effects worked mainly by upregulating GATA3 and downregulating Runx3. These data suggested that Runx3 may play an important role in PM2.5-aggravated asthma in BALB/c mice.

show abstract

Section: Discussionsupporting

confidence: 62%

Fine particulate matter induces airway inflammation by disturbing the balance between Th1/Th2 and regulation of GATA3 and Runx3 expression in BALB/c mice

Pang

Liu

et al. 2021

Mol Med Rep

View full text Add to dashboard Cite

show abstract

“…RUNX3 is known to have tumor suppressive role in gastrointestinal cancers [ 17 , 43 ]. Studies have shown low level of RUNX3 expression in esophageal tumor samples and its expression has been associated with radio-resistance and poor prognosis [ 33 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

Elevated expression of RUNX3 co-expressing with EZH2 in esophageal cancer patients from India

Rehman¹,

Iqbal

Sattar³

et al. 2020

Cancer Cell Int

Self Cite

View full text Add to dashboard Cite

Background Runt related transcription factor3 (RUNX3) is considered as a tumor suppressor gene (TSG) that functions through the TGF-β dependent apoptosis. Promoter methylation of the CpG islands of RUNX3 and overexpression of enhancer of zeste homolog 2 (EZH2) has been suggested to downregulate RUNX3 in cancer. Methods Here, we studied the expression of RUNX3 and EZH2 in 58 esophageal tumors along with paired adjacent normal tissue. mRNA levels, protein expressions and cellular localizations of EZH2 and RUNX3 were analyzed using real-time PCR and immunohistochemistry, respectively. DNA methylation was further assessed by the methylation specific-PCR. Results Compared to normal tissue, a significant increase in expression of RUNX3 mRNA in 31/57 patient’s tumor tissue (p < 0.04) was observed. The expression of EZH2 was found to be upregulated compared to normal, and a significant positive correlation between EZH2 and RUNX3 expression was observed (p = 0.002). 22 of the 27 unmethylated cases at the promoter region of the RUNX3 had elevated RUNX3 protein expression (p < 0.001). Conclusion The data presented in this study provide new insights into the biology of RUNX3 and highlights the need to revisit our current understanding of the role of RUNX3 in cancer.

show abstract

“…The CpG sites (numbers 39–49) were covered by less than 10 trimmed reads in at least one tumor or normal tissue sample and therefore were excluded from the analysis. Non-CpG promoter methylation was recently reported to be a key factor in downregulation of some tumor suppressor genes, e.g., O6-methylguanine-DNA methyltransferase gene and runt-related transcription factor 3 ( Saikia et al, 2017 ). This type of modification is unlikely involved in regulation of ALDH1L1 gene in BC since we failed to determine any hypermethylation of non-CpG sites.…”

Section: Resultsmentioning

confidence: 99%

Deep Sequencing Revealed a CpG Methylation Pattern Associated With ALDH1L1 Suppression in Breast Cancer

et al. 2018

View full text Add to dashboard Cite

Hypermethylation of promoter CpG islands is generally recognized epigenetic mechanism responsible for gene silencing in cancer. However, molecular details on how this epigenetic mark triggers the process of gene downregulation are still elusive. Here, we used deep bisulfite sequencing and qPCR analysis to investigate the pattern of CpG methylation of ALDH1L1 promoter region and its association with the gene expression level in 16 paired breast cancer (BC) samples of different clinical stages. Expression of ALDH1L1 gene was suppressed in all examined BC samples up to 200-fold, and average hypermethylation level of the promoter region correlated positively with ALDH1L1 downregulation. We determined the role of every individual CpG site within the ALDH1L1 promoter, including upstream untranscribed region, first untranslated exon, and the start of the first intron, in aberrant gene expression by correlation analysis. The search revealed CpG sites which methylation has the highest impact on intensity of gene transcription. The majority of such CpG sites are located in a compact region in the first intron of the ALDH1L1 gene. These results assist in unraveling of dynamic nature of CpG promoter hypermethylation as well as demonstrate the efficiency of deep bisulfite sequencing in search for novel epigenetic markers in cancer.

show abstract

Alteration in the expression of MGMT and RUNX3 due to non-CpG promoter methylation and their correlation with different risk factors in esophageal cancer patients

Cited by 8 publications

References 45 publications

Fine particulate matter induces airway inflammation by disturbing the balance between Th1/Th2 and regulation of GATA3 and Runx3 expression in BALB/c mice

Fine particulate matter induces airway inflammation by disturbing the balance between Th1/Th2 and regulation of GATA3 and Runx3 expression in BALB/c mice

Elevated expression of RUNX3 co-expressing with EZH2 in esophageal cancer patients from India

Deep Sequencing Revealed a CpG Methylation Pattern Associated With ALDH1L1 Suppression in Breast Cancer

Contact Info

Product

Resources

About