MiR-495/IGF-1/AKT signaling as a novel axis is involved in the epithelial-mesenchymal transition of oral squamous cell carcinoma

Publication date: Available online 31 December 2018

Source: Journal of Oral and Maxillofacial Surgery

Author(s): Yong Wang, Li Jia, Bin Wang, Shu Diao, Ruizhi Jia, Jiajian Shang

Abstract

Purpose

Increasing evidence suggests that aberrant expression of miR-495 is associated with the progression of various cancers. The aim of this study was to investigate the function and underlying mechanism of miR-495 in oral squamous cell carcinoma (OSCC).

Methods

OSCC specimens and oral cancer cell lines, as well as OSCC miRNA expression profile from the gene expression omnibus database, were used to detect the expression of miR-495 in OSCC. Cell proliferation, migration and invasion assay were performed to analyze the function of miR-495. Bioinformatics and luciferase reporter assays were used to identify the target gene of miR-495. Pearson analysis was carried out to investigate the correlation between miR-495 and IGF-1 or AKT levels. pcDNA3.1 vector and siRNA were transfected to overexpress or downregulate the expression of IGF-1. OSCC xenograft in mice was constructed to validate the function and mechanism of miR-495 in vivo.

Results

MiR-495 was downregulated in OSCC tissues and cell lines, and it significantly inhibited cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) related proteins of OSCC cells. Insulin-like growth factor 1 (IGF-1) was identified as a direct target gene of miR-495. Besides, AKT was confirmed to be regulated by miR-495/IGF-1 signaling, and miR-495 was negatively correlated with IGF-1 and AKT in OSCC. In vivo, miR-495 inhibited the growth and EMT-related proteins of OSCC xenografts in mice.

Conclusion

MiR-495/IGF-1/AKT signaling axis played tumor-suppressive roles in OSCC by regulating cell proliferation, invasion, migration, and epithelial to mesenchymal transition.

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