MicroRNA-4497 functions as a tumor suppressor in laryngeal squamous cell carcinoma via negatively modulation the GBX2.

OBJECTIVE: MicroRNAs (miRNAs) are aberrantly expressed in various tumors and play a critical role in the progression and development of tumors. However, there is little information about the role of miR-4497 in laryngeal squamous cell carcinoma (LSCC). The aim of this study is to investigate the role of miR-4497 in LSCC.

METHODS: MiR-4497 expression in tumor tissues and adjacent normal tissues was measured by RT-PCR. The effects of miR-4497 on cell viability and apoptosis were evaluated by the MTT assay, Flow cytometry and caspase-3 activity assay. Western blot analysis was used to measure the expression of various proteins. Bioinformatic analysis and luciferase reporter assay were applied to investigate the relationship between miR-4497 and GBX2.

RESULTS: We found that miR-4497 expression was downregulated in LSCC tumor tissues and cell lines compared to the normal counterparts. Overexpression of miR-4497 inhibits the proliferation and induces apoptosis of LSCC cells accompanied by the down-regulation of anti-apoptotic Bcl-2 proteins. Mechanisms investigation revealed that GBX2 is a direct target of miR-4497. miR-4497 expression was inversely correlated with GBX2 expression in LSCC tissues. Moreover, overexpression of miR-4497 leads to the activation of ERK, JNK but not p38. Inhibition of ERK by specific inhibitor SCH772984 could interfere the apoptosis induced by overexpression of miR-4497.

CONCLUSION: Therefore, our results indicate that miR-4497 may play a suppressive role in LSCC by targeting GBX2, which offer new insights into the tumorigenesis of LSCC.