MiRNA-485-5p, inhibits esophageal cancer cells proliferation and invasion by down-regulating O-linked N-acetylglucosamine transferase

D.-L. Han, L.-L. Wang, G.-F. Zhang, W.-F. Yang, J. Chai, H.-M. Lin, Z. Fu, J.-M. Yu

Department of Radiation Oncology, Shandong University Affiliated Shandong Cancer Hospital and Institute, Jinan, Shandong Province, China. yujinmingsd8@yeah.net

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• Oncology

OBJECTIVE: Previous reports suggest that miRNA-485-5p is dysregulated and contributes to tumorigenesis in some cancer types. Nevertheless, the biological role of miRNA-485-5p in esophageal cancer (EC) is not well understood. Additionally, we found that the expression of miR-485-5p in EC tissues was aberrant.
PATIENTS AND METHODS: Quantitative RT-PCR (qRT-PCR) was used to demonstrate the expression of miRNA-485-5p in EC cell lines. Cell counting kit-8 (CCK-8) assay and transwell assay indicated that miRNA-485-5p overexpression inhibited cell proliferation, migration, and invasion in EC cell lines. Additionally, Western blotting, dual-luciferase reporter assay, and rescue assay predicted that O-linked N-acetylglucosamine transferase (OGT) was a direct target of miRNA-485-5p. Moreover, we showed that miRNA-485-5p regulated EC tumorigenesis by down-regulating OGT expression in vitro and in vivo.
RESULTS: The upregulation of miR-485-5p (fold change = 44 and 26 in ECA109 and TE-1, respectively; p<0.001) was showed by qRT-PCR. Compared with the control groups, the expression miR-485-5p significantly suppressed the proliferation, migration, and invasion of EC cells. The bioinformatic analysis predicted that the 3’ untranslated region (UTR) of OGT contains one miR-485-5p target sequences. Western blotting and dual-luciferase reporter assay showed that activation of OGT 3’UTR was increased by co-transfection with miR-485-5p. Finally, CCK-8 assay predicted that the rescue effects of OGT expression on miR-485-5p induced inhibition of cell growth and tumor weight in Eca109 and TE1 cells.
CONCLUSIONS: Our results suggest that miRNA-485-5p is a suppressor of EC tumorigenesis and could serve as a novel candidate for therapeutic applications in EC treatment.

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