Newswise — A study in The Journal of Cell Biology reveals that the microRNA miR-7 suppresses gastric (stomach) cancer by inhibiting a key signaling pathway, and that this protective mechanism is compromised by the cancer-causing bacterium H. pylori. Finding drugs capable of inducing miR-7 could therefore prove to be an effective treatment against the progression of gastric cancer.
Gastric cancer is the fourth most common cancer and the third leading cause of cancer-related deaths worldwide, according to the National Institutes of Health. miR-7, which is frequently decreased in gastric cancers, can stop the cancer cells from spreading to other tissues by inhibiting a particular growth factor receptor (called IGF1R). Whether miR-7 also suppresses earlier stages of gastric cancer is unknown, however, so researchers in China screened for new targets of the microRNA.
Dai-Ming Fan and colleagues found that miR-7 directly targets the genes RELA and FOS, which encode proteins involved in the pro-oncogenic NF-κB and AP-1 signaling pathways, respectively. In human gastric cancer samples, low miR-7 levels correlated with elevated levels of RELA and FOS proteins and poor patient survival. Increasing levels of miR-7 reduced RELA and FOS levels and inhibited tumor growth in mice.
The researchers found that, as well as directly suppressing RELA expression, miR-7 could control the protein’s activation by targeting its upstream kinase (IKKε) in the NF-κB pathway. Yet, this same pathway was itself able to repress miR-7 expression, indicating that miR-7 would be unable to restrain RELA’s activity if the NF-κB pathway were strongly activated.
Chronic H. pylori infection is a major risk factor for gastric cancer, in part because the bacterium can hyperactivate the NF-κB pathway. Accordingly, Fan and colleagues found that culturing H. pylori with gastric cells activated IKKε and RELA, and reduced the expression of miR-7, a potentially key step in the transformation of healthy gastric cells into malignant ones.
Zhao, X.-D., et al. 2015. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201501073
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Research reported in the press release was supported by the National Basic Research Program of China, the National Natural Science Foundation of China, the Ministry of Science and Technology of China, and the China Scholarship Council.
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