CagA increases DNA methylation and decreases PTEN expression in human gastric cancer

Baogui Zhang1, Xiaobei Zhang2, Meng Jin1

  • 1Department of Gastrointestinal Surgery, Affiliated Hospital of Jining Medical University, Jining, Shandong 272000, P.R. China.

Molecular Medicine Reports
|November 16, 2018
PubMed

Insights

Cytotoxin-associated gene A (CagA) in gastric cancer reduces tumor suppressor genes PTEN and Tet1. CagA also increases DNA methylation, leading to decreased PTEN, but Tet1 overexpression can reverse this effect.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Gastric cancer is a leading cause of cancer mortality globally.
  • Cytotoxin-associated gene A (CagA) is linked to gastric diseases.
  • PTEN and Tet1 are crucial tumor suppressor genes.

Purpose of the Study:

  • Investigate CagA's function in human gastric cancer.
  • Explore the relationship between CagA, PTEN, and Tet1 in gastric cancer.

Main Methods:

  • Constructed CagA overexpression and Tet1 interference lentiviral plasmids.
  • Utilized qPCR and Western blotting for gene and protein expression analysis.
  • Assessed PTEN methylation status using methylation-specific PCR.

Main Results:

  • CagA overexpression decreased PTEN, Tet1, and APOBEC3 gene/protein expression in HGC-27 cells.
  • Tet1 interference reduced PTEN expression, associated with increased DNA methylation.
  • CagA+ gastric cancer tissues showed decreased PTEN and Tet1 expression compared to non-cancerous tissues.

Conclusions:

  • CagA overexpression significantly downregulates PTEN, Tet1, and APOBEC3 family members in gastric cancer.
  • CagA promotes DNA methylation and reduces PTEN expression, an effect reversible by Tet1.
  • Findings may inform future therapeutic strategies for gastric cancer.

Related Concept Videos

Decreasing Function01:27

Decreasing Function

A decreasing function describes a relationship where the output consistently declines as the input increases. This means that for any two input values, if one is greater than the other, the corresponding output is smaller. Mathematically, a function f is decreasing on an interval I if for every x1 < x2​ in I, f (x1) > f (x2). This type of behavior is visually identified on a graph that slopes downward from left to right.The nature of a function can be analyzed by calculating...
290
Decreased Body Temperature01:29

Decreased Body Temperature

A decreased body temperature can occur in patients with hypothermia and frostbite. Heat loss with extended cold exposure overpowers the body's ability to create heat, resulting in hypothermia. Core temperature readings help classify hypothermia. Mild hypothermia is temperatures between 32 °C (89.6 °F) and 35°C (95 °F) and is caused by impaired thermoregulation. Moderate hypothermia is temperatures between 28 C (82.4 °F) and 32 °C (89.6 °F) caused by...
1.1K
Decreased pulse rate01:14

Decreased pulse rate

Bradycardia is a medical condition in which the heart rate is slower than normal. It occurs when the heart's natural pacemaker, the sinus node, generates slower electrical impulses than the standard rhythm. In adults, bradycardia is diagnosed when the pulse rate falls below 60 beats per minute, indicating a deviation from the normal heart rate range.
There are specific risk factors that can elevate the likelihood of developing bradycardia. Advanced age is a significant factor, with...
902
Gastric Motility01:16

Gastric Motility

Gastric motility is the coordinated contraction and relaxation of stomach muscles that convert ingested food into chyme, a semi-liquid substance ready for further digestion in the intestines. The process begins with the vagus nerve inducing the relaxation of the smooth muscles in the fundus and body of the stomach, allowing these regions to expand and accommodate up to approximately 1.5 liters of food and liquid.
Peristaltic Waves and Chyme Formation
Upon food entry, the stomach initiates...
3.2K
Gastric Emptying01:16

Gastric Emptying

Gastric emptying occurs when the stomach gradually releases chyme into the duodenum. When the stomach is distended, it triggers the release of gastrin, a hormone that promotes gastric acid secretion to aid in digestion. Additionally, stomach distension contributes to peristaltic waves that propel gastric contents toward the pyloric region. The gastroenteric reflex, on the other hand, primarily stimulates peristalsis in the intestines, facilitating the movement of contents further along the...
3.7K
Increasing Function01:18

Increasing Function

An increasing function exhibits a rise in output values as input values increase. This behavior is depicted graphically as a curve or line that slopes upward from left to right. Such a function satisfies the condition that if x1 < x2, then f(x1) < f(x2), indicating that the function values grow with increasing inputs. This concept is fundamental in understanding growth trends across various domains, such as population dynamics, financial investments, or resource consumption.The...
394