Abstract
Tristetraprolin (TTP) is an mRNA-binding protein that can induce mRNA degradation. It controls cell growth and factors related to tumor development by binding AU-rich elements located in the 3' untranslated region (UTR) of mRNA, leading to rapid mRNA decay. Resveratrol, which is a natural flavonoid polyphenolic compound, has been shown to exert biological activities on various human cancers. However, there are no studies assessing its effects with TTP regulation on human gastric cancer. The present novel study demonstrated that the tumor suppressing effects of resveratrol were mediated via the induction of TTP expression in gastric cancer. We found that resveratrol induced TTP mRNA and protein expression in the gastric cancer cell lines SNU484 and SNU638. Treatment with resveratrol enhanced the decaying activity of TTP on luciferase mRNA containing cIAP2, LATS2, Lin28, and E2F1 in their 3' UTR. We also confirmed that TTP was upregulated. Target genes of TTP (E2F1, LATS2, and Lin28) were downregulated by resveratrol treatment in SNU484 cells as observed in a microarray experiment. Furthermore, we observed that resveratrol affects cell proliferation, metastasis, and tumor formation in SNU484 and SNU638 cells. Overall, the results of the present study suggest that resveratrol induced the mRNA and protein levels of TTP by regulating the decay of cIAP2, LATS2, Lin28, and E2F1 mRNA. It can thus be concluded that resveratrol can be utilized as a potential therapeutic anticancer agent for treating human gastric cancer.
Highlights
Gastric cancer is one of the most fatal cancers and is the second leading cause of cancer-related deaths worldwide [1-4]
We determined that the TTP expression was induced by resveratrol in a dose-dependent manner in gastric cancer cells
As our previous studies showed that TTP reduced the expression of cIAP2, E2F1, LATS2, and Lin28 mRNA and inhibited the growth of various cancer cells, we further examined whether TTP regulates the stabilities of target genes in gastric cancer cells
Summary
Gastric cancer is one of the most fatal cancers and is the second leading cause of cancer-related deaths worldwide [1-4]. The highest incidence of and mortality rates due to gastric cancer are found in eastern and western Asian countries including South Korea. The incidence of gastric cancer in South Korea has been observed to be 60-64% higher than in Asian countries with the highest incidence [4,5]. Developing a new classification system for gastric cancer and understanding the molecular pathogenesis of gastric cancer are required for to develop effective therapeutic approaches. In this way, a promising new method could be established that may help further reduce gastric cancer incidence and mortality rates. It is urgent to identify novel therapeutic targets and preventive treatments to control the high mortality rates due to gastric cancer
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