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Expressional profiles of transcription factors in the progression of Helicobacter pylori-associated gastric carcinoma based on protein/DNA array analysis

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Abstract

Transcription factors (TFs) are crucial modulators of gene expression during the development and progression of gastric carcinoma. Helicobacter pylori (H. pylori) is one of the most significant risk factors of gastric carcinoma, and it is widely known that chronic inflammation with H. pylori infection triggers gastric carcinogenesis through inflammation-carcinoma chain [gastric carcinogenesis stages: non-atrophic gastritis, chronic atrophic gastritis, intestinal metaplasia, dysplasia and gastric carcinoma (GC)], but its mechanism regarding changed TFs remains unknown. In this study, we investigated the expressional profiles of 345 transcription factors in gastric mucosa of healthy volunteers and patients at different gastric carcinogenesis stages using protein/DNA array-based approach. The data demonstrated the up-regulated TFs such as GATA-3, AP4, c-Myc and Pbx1 in the gastric mucosa of GC patients compared with the healthy volunteers, while other TFs, particularly CCAAT and CACC, showed the consistently decreasing trend along the gastric carcinogenesis. The increased expressions of AP4, Pbx1 and C/EBPα were further validated by quantitative real-time PCR and Western blot in various H. pylori-infected models such as clinical gastric tissues, gastric epithelial cell lines and Mongolian gerbils. This study provides insights into and potential laws for gene transcriptional regulation by identifying potential TFs targets against the development of H. pylori-associated gastric carcinoma.

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Abbreviations

H. pylori :

Helicobacter pylori

TFs:

Transcription factors

NGM:

Normal gastric mucosa

NAG:

Non-atrophic gastritis

CAG:

Chronic atrophic gastritis

IM:

Intestinal metaplasia

DYS:

Dysplasia

PLGC:

Precancerous lesions of gastric cancer

GC:

Gastric carcinoma

CagA:

Cytotoxin-associated gene A

VacA:

Vacuolating cytotoxin gene A

GATA-3:

GATA-binding protein 3

AP4:

Activator protein 4 binding element

Pbx1:

Pre-B-cell leukemia transcription factor 1

C/EBP α:

CCAAT/enhancer-binding protein α

CCAAT-BP:

CCAAT-binding protein

CACC-BP:

CACC-binding protein

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Acknowledgments

This study is supported by a Grant from the National Natural Science Foundation of China (No. 81172301).

Author contributions

Hu T analyzed the data and wrote the manuscript; Huang L guided the analysis and manuscript writing; Xu CX designed the study, performed the endoscopic procedures, collected specimens and revised the manuscript; Liu X, Xiao J and Zhou L conducted the cell and Helicobacter pylori experiments; Wang Y collected and sent the specimens for array analysis; Luo L and Jiang X performed the experiment of Mongolian gerbils.

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Authors and Affiliations

  1. Department of Gastroenterology, Third Xiangya Hospital of Central South University, 138 Tongzipo Street, Changsha, 410013, Hunan Province, China

    Ting-Zi Hu, Can-Xia Xu, Xiao-Ming Liu, Jing Xiao, Li Zhou, Ling Luo & Xiao-Xia Jiang

  2. Center for Medical Experiment, Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan Province, China

    Li-Hua Huang

  3. Department of Internal Medicine, The Third People’s Hospital of Huaihua, Huaihua, 418000, Hunan Province, China

    Yu Wang

  4. Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, 410013, China

    Can-Xia Xu

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  1. Ting-Zi Hu
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  2. Li-Hua Huang
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  3. Can-Xia Xu
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  4. Xiao-Ming Liu
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  7. Li Zhou
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  9. Xiao-Xia Jiang
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Correspondence to Can-Xia Xu.

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Hu, TZ., Huang, LH., Xu, CX. et al. Expressional profiles of transcription factors in the progression of Helicobacter pylori-associated gastric carcinoma based on protein/DNA array analysis. Med Oncol 32, 265 (2015). https://doi.org/10.1007/s12032-015-0711-y

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