Reduced mRNA expression levels of MBD2 and MBD3 in gastric carcinogenesis

Thaís Brilhante Pontes1, Elizabeth Suchi Chen, Carolina Oliveira Gigek

  • 1Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, Rua Botucatu, 740 - Ed. Leitão da Cunha - 1ºandar, São Paulo, 04023-900, SP, Brazil.

Insights

Reduced expression of methyl-CpG-binding domain (MBD) proteins MBD2 and MBD3 is linked to gastric cancer development. DNA methylation appears to play a minor role in regulating these genes in gastric carcinogenesis.

Area of Science:

  • Molecular Oncology
  • Epigenetics
  • Gastric Carcinogenesis

Background:

  • Aberrant DNA methylation is a hallmark of various cancers, including gastric cancer.
  • Methyl-CpG-binding domain (MBD) proteins are crucial for chromatin remodeling and gene expression regulation.
  • The specific roles of MBD2 and MBD3 in gastric carcinogenesis remain incompletely understood.

Purpose of the Study:

  • To investigate the messenger RNA (mRNA) levels and promoter methylation patterns of MBD2 and MBD3 in gastric tissues.
  • To evaluate the association between MBD2 and MBD3 expression and clinicopathological characteristics in gastric cancer.
  • To elucidate the potential role of DNA methylation in regulating MBD2 and MBD3 expression during gastric carcinogenesis.

Main Methods:

  • Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to determine MBD2 and MBD3 mRNA levels.
  • Bisulfite sequencing was employed to analyze the promoter methylation status of MBD2 and MBD3.
  • Samples included neoplastic gastric tissues, adjacent nonneoplastic tissues, gastritis, and non-gastritis tissues.

Main Results:

  • Significantly reduced MBD2 and MBD3 mRNA levels were observed in neoplastic gastric tissues compared to other groups.
  • Neoplastic tissues displayed higher MBD2 promoter methylation, while MBD3 promoter methylation was notable in the non-gastritis group.
  • A strong correlation was found between MBD2 and MBD3 expression levels, but a weak correlation between gene expression and promoter methylation.

Conclusions:

  • Reduced mRNA expression of MBD2 and MBD3 is implicated in gastric carcinogenesis.
  • DNA methylation appears to play a limited role in the direct regulation of MBD2 and MBD3 expression in this context.
  • Further research is warranted to fully understand the epigenetic mechanisms, including methylation at specific CpG sites, involved in gastric neoplasia.

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.0K
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.1K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
21.1K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.0K
Gastritis II: Pathophysiology01:26

Gastritis II: Pathophysiology

The pathophysiology of gastritis begins with the colonization of the stomach lining by Helicobacter pylori (H. pylori). This bacterium spreads mainly via the oral-oral route through saliva or shared utensils, and can also be transmitted in overcrowded or unhygienic environments through contaminated water, despite its brief survival outside the body.ColonizationOnce ingested, H. pylori enters the stomach and begins colonization by navigating through the mucus layer lining the stomach wall. It...
52
Pathophysiology of Peptic Ulcer Disease: Mucosal Defense Factors01:24

Pathophysiology of Peptic Ulcer Disease: Mucosal Defense Factors

Peptic ulcer disease, commonly called PUD, represents a multifaceted condition characterized by disruptions in the lining of the gastrointestinal (GI)  tract. Central to the protection of the gastrointestinal lining is the mucosal-bicarbonate barrier. This physiological defense mechanism is a formidable shield against the corrosive effects of gastric acid and pepsin secretion in the stomach. Its role is pivotal in maintaining the structural integrity of the stomach's inner lining.
1.6K