Inhibition of microRNA-15b-5p Attenuates the Progression of Oral Squamous Cell Carcinoma via Modulating the PTPN4/STAT3 Axis

Background: Emerging evidence has demonstrated the important functions of MicroRNAs (miRNAs) in human malignancies. This study focuses on the function of miR-15b-5p on the oral squamous cell carcinoma (OSCC) progression and the molecules involved.

Methods: Tumor and the paracancerous tissues were obtained from OSCC patients. Differentially expressed miRNAs between the tumor and normal tissues were screened out. miR-15b-5p expression in tumors and acquired cells was determined, and its correlation with patient survival was analyzed. Knockdown of miR-15b-5p was introduced in SCC-4 and CAL-27 cells to explore its role in cell growth and metastasis. Binding relationship between miR-15b-5p and PTPN4 was validated, and altered expression of PTPN4 was introduced in cells to explore its function in OSCC development. Xenograft tumors were induced in nude mice for in vivo experiments.

Results: miR-15b-5p was abundantly expressed in OSCC tumors and cells and linked to poor survival in patients. Silencing of miR-15b-5p suppressed proliferation, migration, and invasion and triggered Apoptosis in SCC-4 and CAL-27 cells. miR-15b-5p targeted PTPN4. Further silencing of PTPN4 blocked the inhibiting functions of miR-15b-5p inhibitor in OSCC cell growth. The in vitro results were reproduced in vivo, where inhibition of miR-15b-5p led to a decline in tumor growth and metastasis in nude mice. PTPN4 was found as a negative mediator of the STAT3 pathway.

Conclusion: This study evidenced that miR-15b-5p possibly promotes OSCC development through binding to PTPN4 and the following STAT3 signaling activation. miR-15b-5p may be a potential therapeutic target for OSCC.