Neoplasma Vol.69, No.3, p.550–559, 2022
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| Title: 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 |
| Author: Fu Chen, Zheng Lao, Hai-Yan Zhang, Jie Wang, Sheng-Zi Wang |
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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, microRNA (miRNA) plays 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. Overexpression 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.
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| Keywords: laryngeal squamous cell carcinoma; miR-125b-5p; MAP3K9; proliferation; apoptosis; glycolysis |
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Published online: 21-Feb-2022
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| Year: 2022, Volume: 69, Issue: 3 |
Page From: 550, Page To: 559 |
doi:10.4149/neo_2022_211027N1532
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