Elevation of miR-125b-5p is related to improved prognosis in laryngeal squamous cell carcinoma and inhibits the malignancy and glycometabolic disorder by targeting MAP3K9

Abstract

Laryngeal squamous cell carcinoma (LSCC) is the most common malignant tumor in the head and neck cancer, with a poor prognosis. As we know, microRNAs (miRNAs) play a vital role in the initiation and development of various cancers including LSCC. In this study, we explored the role of miR-125b-5p and its downstream regulatory pathway in LSCC. Our data demonstrated that miR-125b-5p expression was significantly downregulated in LSCC tissues and cells. LSCC patients with high expression of miR-125b-5p had higher overall survival (OS) and were closely related to the clinical stage. Overexpression of miR-125b-5p impaired viability and glycolysis, and facilitated apoptosis in LSCC cells. And miR-125b-5p silencing had the opposite effects. Bioinformatics website predicted that MAP3K9 was one of the potential target genes of miR-125b-5p. Cell experiments demonstrated that miR-125b-5p repressed the MAP3K9 levels by directly targeting MAP3K9. Additionally, the negative correlation between miR-125b-5p and MAP3K9 was validated in LSCC tissues. Overex-pression of MAP3K9 attenuated the inhibitory effect of miR-125b-5p on viability and glycolysis, and the pro-apoptosis effect of miR-125b-5p in LSCC cells. Furthermore, in vivo experiments demonstrated that tumor growth was hampered in AMC-HN-8 cells transfected with miR-125b-5p mimic. In contrast, the knockdown of miR-125b-5p reduced tumor growth in vivo. Meanwhile, the in vivo immunohistochemistry and TUNEL assays suggested that the miR-125b-5p overexpression restrained cell proliferation and promoted apoptosis via targeting MAP3K9. Overall, these above results suggested that miR-125b-5p suppressed proliferation and glycolysis, and promoted apoptosis by directly targeting MAP3K9 in LSCC cells. Thus, miR-125b-5p acts as a tumor suppressor miRNA and the miR-125b-5p/MAP3K9 axis may be a promising candidate for LSCC treatment.