Abstract
Purposes
Uncontrolled proliferation is a key characteristic of gastric carcinogenesis and the precise mechanisms underlying the altered proliferation behaviors of GC cells have not been clearly elucidated. miRNAs has been suggested to play a crucial role in the pathogenesis and development of various cancers. In the present study, we employed an impedance-based real-time cell electronic sensing (RT-CES) system to detect the effects of ectopically expressed miRNAs on GC cell proliferation.
Methods
miRNA mimics were transfected into gastric cancer cell line SGC7901 and the effect of individual miRNA on the proliferation rate of the cells was measured by the RT-CES system. The screening results were validated with qRT-PCR and miR-137 was selected for further research. The effects of ectopically expressed miR-137 on GC cell growth and cell cycle progress were measured using MTT assay and flow cytometry. The target gene of miR-137 was predicted using different bioinformatics tools and the direct interaction between miR-137 and the 3’-UTR was confirmed with a luciferase reporter assay. The in vivo effect of miR-137 on GC cell proliferation was examined with a tumor-bearing nude mouse model. The correlation between miR-137 expression and patients’ prognosis was explored in a cohort of 38 patients. Prognosis was explored in a cohort of 38 patients.
Results
Ectopic expression of miR-137 was sufficient to inhibit GC cell proliferation both in vitro and in vivo. Bioinformatics prediction and luciferase reporter assay revealed CDK6 as a target gene through which miR-137 exerted an inhibitory function. Moreover, miR-137 expression positively correlated with better prognosis.
Conclusion
Our data indicated an important regulatory role of miR-137 in GC cell proliferation and that it may be explored as a prognostic marker for GC.
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Xiushan Zheng, Jiaqiang Dong, Taiqian Gong and Zhiyong Zhang have contributed equally to this work.
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Zheng, X., Dong, J., Gong, T. et al. MicroRNA library-based functional screening identified miR-137 as a suppresser of gastric cancer cell proliferation. J Cancer Res Clin Oncol 141, 785–795 (2015). https://doi.org/10.1007/s00432-014-1847-4
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DOI: https://doi.org/10.1007/s00432-014-1847-4