MicroRNA-7 may modulate gastric carcinogenesis

Reuters Health Information: MicroRNA-7 may modulate gastric carcinogenesis

MicroRNA-7 may modulate gastric carcinogenesis

Last Updated: 2015-08-17

By Reuters Staff

NEW YORK (Reuters Health) - Activity involving microRNA-7 (miR-7) may regulate gastric cancer (GC) development and progression, and Helicobacter pylori could influence this process, according to Chinese researchers.

In an August 10 online paper in the Journal of Cell Biology, Dr. Dai Ming Fan of Xijing Hospital of Digestive Diseases, Shaanxi, and colleagues noted, "Because each miRNA is estimated to target several hundred distinct genes, their roles are conceivably as important as transcription factors or signaling molecules in controlling various cellular processes."

In particular, the team had earlier found that miR-7 inhibits certain metastatic GC cells, and to gain more information, they used genome-wide screenings and found that important targets were RELA and FOS. These genes encode proteins involved in pro-oncogenic nuclear factor-kappa B (NF-kappa B) and other signaling.

In xenografts in nude mice, miR-7 overexpression significantly reduced RELA and FOS expression and decreased tumor growth. The inhibition of miR-7 promoted tumor growth and levels of RELA and FOS expression.

Study of human CG cells showed that miR-7 was reduced in almost all GC tissues compared with normal tissues, and a low expression of miR-7 in GC patients was associated with advanced tumor node metastasis stage and shorter survival.

The team further found that miR-7 could indirectly regulate RELA activation via the NF-kappa B pathway. However, this pathway was itself able to repress miR-7 expression.

The researchers also pointed out that H. pylori infection, a major risk factor for gastric cancer, can induce aberrant NF-kappa B activation and cause chronic inflammation. In fact, co-culture of gastric epithelial cells with H. pylori resulted in a pronounced induction of RELA, which was accompanied by a repression of miR-7 expression.

This novel miR-7/NF-kappa B signaling circuitry, the investigators concluded, may be "a new mechanism of gastric carcinogenesis and hold promise for the development of potential therapeutics against GC."

Dr. Fan and coauthors did not respond to requests for comment.

The National Basic Research Program of China, the National Natural Science Foundation, the Ministry of Science and Technology, and the China Scholarship Council supported this research. The authors reported no disclosures.

SOURCE: http://bit.ly/1TMxwTi

J Cell Biol 2015.

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