Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 22, Issue 10, Pages 4721-4731Publisher
WILEY
DOI: 10.1111/jcmm.13716
Keywords
epigenetic silence; gastric cancer; miR-125a-5p; Suv39H1
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Funding
- Novel Project of Fujian Medicine [2014-CXB-29]
- Natural Science Foundation of Zhangzhou [ZZ2018J05]
- Startup Fund for scientific research of Fujian Medical University [2017XQ1113]
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Emerging evidence suggests that microRNAs (miRNAs) serve an important role in tumorigenesis and development. Although the low expression of miR-125a-5p ingastric cancer has been reported, the underlying mechanism remains unknown. In the current study, the low expression of miR-125a-5p in gastric cancer was verified in paired cancer tissues and adjacent non-tumour tissues. Furthermore, the GC islands in the miR-125a-5p region were hypermethylated in the tumour tissues. And the hypermethylation was negatively correlated with the miR-125a-5p expression. Target gene screening showed that the histone methyltransferase Suv39H1 was one of the potential target genes. In vitro studies showed that miR-125a-5p could directly suppress the Suv39H1 expression and decrease the H3K9me3 levels. On the other hand, the Suv39H1 could induce demethylation of miR-125a-5p, resulting in re-activation of miR-125a-5p. What is more, overexpessing miR-125a-5p could also self-activate the silenced miR-125a-5p in gastric cancer cells, which suppressed cell migration, invasion and proliferation invitro and inhibited cancer progression invivo. Thus, we uncovered here that the epigenetic silenced miR-125a-5p could be self-activated through targeting Suv39H1 in gastric cancer, suggesting that miR-125a-5p might be not only the potential prognostic value as a tumour biomarker but also potential therapeutic targets in gastric cancer.
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