Helicobacter pyloriInduces Increased Expression of Toll-Like Receptors and Decreased Toll-Interacting Protein in Gastric Mucosa that Persists Throughout Gastric Carcinogenesis

It is known that gastric carcinogenesis results from the progressive changes from chronic gastritis to gastric atrophy, intestinal metaplasia, dysplasia, and invasive carcinoma. Several genetic and epigenetic alterations are involved in this process, and Helicobacter pylori (H. pylori) infection is believed to induce the initiation and progression of these steps. From an epigenetic point of view, H. pylori induces hypermethylation of genes involved in the development of gastric cancer and regulates the expression of various microRNAs (miRNAs). These H. pylori-related epigenetic changes are accumulated not only at the site of neoplasm but also in the adjacent non-cancerous gastric mucosa. Thereby, a state vulnerable to gastric cancer known as an epigenetic field defect is formed. H. pylori eradication can have an effective chemopreventive effect in gastric carcinogenesis. However, the molecular biological changes that occur in the stomach environment during H. pylori eradication have not yet been established. Several studies have reported that H. pylori eradication can restore infection-related changes, especially epigenetic alterations in gastric cancer-related genes, but some studies have shown otherwise. Simply put, it appears that the recovery of methylated gastric cancer-related genes and miRNAs during H. pylori eradication may vary among genes and may also differ depending on the histological subtype of the gastric mucosa. In this review, we will discuss the potential mechanism of gastric cancer prevention by H. pylori eradication, mainly from an epigenetic perspective.

Download Full-text

Toll-Like Receptors are Associated with Helicobacter pylori Infection and Gastric Mucosa Pathology

Jundishapur Journal of Microbiology ◽

10.5812/jjm.58351 ◽

2017 ◽

Vol 10 (12) ◽

Cited By ~ 1

Author(s):

Theeraya Simawaranon ◽

Wareeporn Wattanawongdon ◽

Taweesak Tongtawee

Keyword(s):

Helicobacter Pylori ◽

Gastric Mucosa ◽

Helicobacter Pylori Infection ◽

Toll Like Receptors

Download Full-text

Differential expression of human telomerase reverse transcriptase β-site remaining alternative splicing variants (hTERT β+ ASV) in gastric carcinogenesis

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e15641 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e15641-e15641

Author(s):

X. Geng

Keyword(s):

Gastric Cancer ◽

Enzyme Activity ◽

Alternative Splicing ◽

Gastric Mucosa ◽

Precancerous Lesions ◽

Normal Mucosa ◽

Gastric Carcinogenesis ◽

Normal Gastric Mucosa ◽

Rt Pcr ◽

Splicing Variants

e15641 Background: To investigate the changes of hTERT alternative splicing variants pattern in gastric cancer, precancerous lesions and normal gastric mucosa tissue. Methods: Three alternative splicing sites (α, β, γ) were selected and designed PCR primer. The expression of 8 hTERT alternative splicing variants (ASVs) in gastric cancer, precancerous lesions and normal gastric mucosa were detected by Semi-nested RT-PCR. The expression of β-site remaining ASV (β+ASV) in specimens of gastric cancer and specimens of precancerous lesions was detected by SYBER Green real-time PCR. Telomerase enzyme activity was evaluated associated with the different hTERT ASVs. Results: The positive rate of active full-length (α+β+γ+ ) ASV was significantly higher in gastric cancer than in precancerous lesions and normal mucosa (94.7% vs. 40.0% and 0, P<0.05). The positive rates of other ASVs were not different among the 3 groups(P>0.05). The positive rates of β+ ASVs (including α+β+γ+ASV, α-deletion ASV, γ-deletion ASV, αγ-deletion ASV) were 11.1% in normal mucosa,40.0% in precancerous lesions and 94.7% in gastric cancer (P<0.05). SYBR Green real-time RT-PCR showed that the expression level of β+ASV was 6.99 times higher in gastric cancer than in precancerous lesions. Further, increased telomerase enzyme activity was only associated with expression of the full-length hTERT isoform. Conclusions: hTERT alternative splicing pattern is different during gastric carcinogenesis. β+ASV was widely expressed in gastric carcinogenesis and may provide some information for diagnosis of gastric cancer or precancerous lesions. The gene expression patterns of hTERT alternative splicing variants may provide some useful information for diagnosis of gastric cancer and precancerous lesions. No significant financial relationships to disclose.

Download Full-text