PMID- 35188403 OWN - NLM STAT- MEDLINE DCOM- 20220609 LR - 20220615 IS - 0028-2685 (Print) IS - 0028-2685 (Linking) VI - 69 IP - 3 DP - 2022 May TI - 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. PG - 550-559 LID - 211027N1532 [pii] LID - 10.4149/neo_2022_211027N1532 [doi] AB - 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. 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. FAU - Chen, Fu AU - Chen F AD - Department of Radiation Oncology, Eye and ENT Hospital of Fudan University, Shanghai, China. FAU - Lao, Zheng AU - Lao Z AD - Radiotherapy Division, Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Zhang, Hai-Yan AU - Zhang HY AD - Department of Radiation Oncology, Eye and ENT Hospital of Fudan University, Shanghai, China. FAU - Wang, Jie AU - Wang J AD - Department of Radiation Oncology, Eye and ENT Hospital of Fudan University, Shanghai, China. FAU - Wang, Sheng-Zi AU - Wang SZ AD - Department of Radiation Oncology, Eye and ENT Hospital of Fudan University, Shanghai, China. LA - eng PT - Journal Article DEP - 20220222 PL - Slovakia TA - Neoplasma JT - Neoplasma JID - 0377266 RN - 0 (MIRN125 microRNA, human) RN - 0 (MicroRNAs) RN - EC 2.7.11.25 (MAP Kinase Kinase Kinases) RN - EC 2.7.11.25 (MAP3K9 protein, human) SB - IM MH - Cell Line, Tumor MH - Cell Proliferation/genetics MH - Humans MH - *Laryngeal Neoplasms/pathology MH - *MAP Kinase Kinase Kinases/genetics/metabolism MH - *MicroRNAs/biosynthesis/genetics/metabolism MH - Prognosis MH - *Squamous Cell Carcinoma of Head and Neck EDAT- 2022/02/22 06:00 MHDA- 2022/06/10 06:00 CRDT- 2022/02/21 12:10 PHST- 2021/10/27 00:00 [received] PHST- 2022/01/17 00:00 [accepted] PHST- 2022/02/22 06:00 [pubmed] PHST- 2022/06/10 06:00 [medline] PHST- 2022/02/21 12:10 [entrez] AID - 211027N1532 [pii] AID - 10.4149/neo_2022_211027N1532 [doi] PST - ppublish SO - Neoplasma. 2022 May;69(3):550-559. doi: 10.4149/neo_2022_211027N1532. Epub 2022 Feb 22.