Gastric cancer (GC) is one of the most lethal cancers worldwide. In this study, we aimed to explore the role of miR-129-5p, a newly identified miR-129 member, in GC cells as well as the potential mechanism of action. The results of reverse transcription - qualitative polymerase chain reaction (RT-qPCR) and Western Blot showed that miR-129 was downregulated in GC cells compared with normal ones. Using MTT, colony formation, wound healing assay, and a Transwell assay, we evaluated the proliferation, migration, and invasion abilities of transfected cells, and confirmed miR-129-5p as a tumor suppressor in GC. After a microarray analysis comparing different gene expressions in miR-129-5p transfected SGC-7901 cells, COL1A1 was selected for biggest fold-change and potential target of miR-129-5p predicted by TargetScan. Measured by RT-qPCR and Western blot, COL1A1 turned out to be upregulated in GC tissues and cells. We further confirmed the targeting relationship between miR-129-5p and COL1A1 by dual luciferase assay. By manipulating the expression of COL1A1 in SGC-7901 cells, cell proliferation, migration, and invasion were examined and the tumor-promoting function of COL1A1 was validated. Moreover, co-transfection of miR-129-5p mimics and COL1A1 attenuated the tumor-promoting effects induced by a single-transfection of COL1A1, and miR-129-5p inhibitor counteracted the tumor-suppressing effects of COL1A1 siRNA. Collectively, the data demonstrate the important functions of the miR-129-5p-COL1A1 axis in GC: miR-129-5p suppresses GC cell proliferation, migration, and invasion, by selectively inhibiting COL1A1. This study provides new therapeutic targets for the clinical treatment of GC.
Environmental stress-mediated adaptation plays essential roles in the evolution of life. Cellular adaptation mechanisms usually involve the regulation of chromatin structure, transcription, mRNA stability and translation, which eventually lead to efficient changes in gene expression. Global epigenetic change is also involved in the reprogramming of somatic cells into induced pluripotent stem (iPS) cells by defined factors. Here we report that environmental stress such as hyperosmosis not only facilitates four factor-mediated reprogramming, but also enhances two or one factor-induced iPS cell generation. Hyperosmosis-induced p38 activation plays a critical role in this process. Constitutive active p38 mimics the positive effect of hyperosmosis, while dominant negative p38 and p38 inhibitor block the effect of hyperosmosis. Further study indicates stress-mediated p38 activation may promote reprogramming by reducing the global DNA methylation level and enhancing the expression of pluripotency genes. Our results demonstrate how simple environmental stress like hyperosmosis helps to alter the fate of cells via intracellular signaling and epigenetic modulation.
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