The microRNA-34b-3p/SOX5 axis regulates cellular activities and tumor angiogenesis in oral squamous cell carcinoma

Abstract

Objective

This study aimed to ascertain the significance of microRNA-34b-3p (miR-34b-3p) in the prognosis and tumor angiogenesis associated with the development of oral squamous cell carcinoma (OSCC).

Design

The relative abundances of miR-34b-3p and tumor angiogenesis-associated genes were quantified using quantitative real-time polymerase chain reaction. Cellular events were monitored using the Cell Counting Kit-8 and Transwell assays. Additionally, a luciferase reporter assay was carried out to verify the interaction between miR-34b-3p and Sex Determining Region Y-box Protein 5 (SOX5).

Results

MiR-34b-3p was significantly decreased in tissue samples from OSCC patients in comparison to healthy individuals (P < 0.001) and displayed a robust diagnostic accuracy in distinguishing OSCC patients from healthy controls. Moreover, OSCC patients expressing low miR-34b-3p levels displayed a short overall survival time (P = 0.002). Additionally, low miR-34b-3p expression was an independent predictor for the clinical outcome of OSCC patients (P = 0.011, HR=0.447, 95 %CI=0.239–0.834). Through biological experiments, downregulation of miR-34b-3p could promote cell proliferation, migration and invasion of OSCC cells. Notably, following transfection miR-34b-3p inhibitor, VEGFA and MMP9 mRNA expressions were dramatically enhanced (P < 0.001). SOX5 was identified as a potential target of miR-34b-3p. Recovery experiments verified that the knockdown of SOX5 counteracted the impacts of miR-34b-3p on cellular activities and angiogenesis.

Conclusions

Downregulated miR-34b-3p expression promoted OSCC progression by enhancing cellular activities and upregulating the expression of pro-angiogenic factors via targeting SOX5.