Related Experiment Video

Updated: Jun 17, 2026

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
07:50

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer

Published on: September 18, 2020

Involvement of epigenetically silenced microRNA-181c in gastric carcinogenesis

Yutaka Hashimoto1, Yoshimitsu Akiyama, Takeshi Otsubo

  • 1Department of Molecular Oncology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.

Carcinogenesis
|January 19, 2010
PubMed

Insights

MicroRNA (miRNA) dysregulation is common in cancer. This study shows miR-181c, a microRNA, is silenced by methylation in gastric cancer, inhibiting tumor growth by targeting NOTCH4 and KRAS.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Aberrant microRNA (miRNA) expression is implicated in various cancers, including gastric cancer.
  • Understanding miRNA roles in gastric carcinogenesis is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the role of miRNA in gastric carcinogenesis.
  • To identify specific miRNAs affected by epigenetic modifications in gastric cancer cells.

Main Methods:

  • MicroRNA microarray analysis of 5-aza-2'-deoxycytidine (5-aza-CdR)-treated gastric cancer cells (KATO-III).
  • Reverse transcription-polymerase chain reaction (RT-PCR) to verify miRNA upregulation.
  • Analysis of CpG islands and methylation in miRNA upstream sequences.
  • Cell growth assays and target gene identification using cDNA microarray and reporter assays.

Main Results:

  • Five miRNAs were upregulated after 5-aza-CdR treatment, including miR-181c and miR-432AS.
  • miR-181c upregulation was confirmed in multiple cancer cell lines and was decreased in primary gastric carcinoma (GC) tissues.
  • Hypermethylation in the miR-181c upstream region correlated with low/negative expression in GC cells.
  • miR-181c precursor transfection inhibited gastric cancer cell growth.
  • NOTCH4 and KRAS were identified as direct targets of miR-181c.

Conclusions:

  • miR-181c may be epigenetically silenced by methylation in gastric cancer.
  • miR-181c acts as a tumor suppressor in gastric carcinogenesis by targeting oncogenes NOTCH4 and KRAS.

Related Concept Videos

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...
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...
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 ends...
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
Genomic Imprinting and Inheritance02:30

Genomic Imprinting and Inheritance

Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...