Abstract
Background
MiR-141 and long noncoding RNA MEG3 have been independently reported to be tumor suppressor genes in various cancers. However, their expression has never been previously associated with gastric cancer (GC).
Aims
To investigate the interaction of miR-141 and MEG3 in GC.
Methods
QRT-PCR was used to detect miR-141, MEG3, and E2F3 in gastric tissues and cells. CCK-8 and flow cytometry analysis were used to detect cell functions. Western blot and luciferase activity were used to identify E2F3 as one of the direct targets of miR-141.
Results
We found that expression of both miR-141 and MEG3 was significantly reduced in GC compared with levels in matched nonmalignant tissues. Positive correlation between miR-141 and MEG3 was found in both tumor tissues and control tissues. Furthermore, the over-expression of either miR-141 or MEG3 in 7901 and MKN45 cells inhibited cell proliferation and cell cycle progression and promoted cell apoptosis. E2F3 was identified as a target of miR-141, and its inhibition significantly reduced MEG3 expression. E2F3 expression was also found to be negatively associated with both MEG3 and miR-141. E2F3 over-expression partly reversed the changes caused by transfection of miR-141 mimic, and inhibition of miR-141 or MEG3 overrides MEG3- or miR-141-induced modulation of cell growth in GC.
Conclusions
These findings together suggested that miR-141 could be interacting with MEG3 and targeting E2F3, and these factors may play important anti-tumor effects in GC pathogenesis and provide therapeutic targets in the clinics.
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Acknowledgments
This work was supported by National Natural Science Foundation of China (No. 81470830), the Priority Academic Program Development of Jiangsu Higher Education Institutions (JX10231801), and Jiangsu postgraduate scientific research and innovation projects (CXZZ13_0574).
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Xiaoying Zhou, Guoping Ji, and Huiyuan Gu have contributed equally to this work.
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Zhou, X., Ji, G., Ke, X. et al. MiR-141 Inhibits Gastric Cancer Proliferation by Interacting with Long Noncoding RNA MEG3 and Down-Regulating E2F3 Expression. Dig Dis Sci 60, 3271–3282 (2015). https://doi.org/10.1007/s10620-015-3782-x
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DOI: https://doi.org/10.1007/s10620-015-3782-x