Department of Radiation Oncology, Eye and ENT Hospital of Fudan University, Shanghai, China.
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.
Neoplasma. 2022 May;69(3):550-559. doi: 10.4149/neo_2022_211027N1532. Epub 2022 Feb 22.
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.
喉鳞状细胞癌（LSCC）是头颈部癌症中最常见的恶性肿瘤，预后较差。众所周知，microRNAs（miRNAs）在包括 LSCC 在内的各种癌症的发生和发展中起着至关重要的作用。在这项研究中，我们探讨了 miR-125b-5p 及其下游调控途径在 LSCC 中的作用。我们的数据表明，miR-125b-5p 在 LSCC 组织和细胞中的表达明显下调。miR-125b-5p 高表达的 LSCC 患者总生存率（OS）更高，且与临床分期密切相关。miR-125b-5p 的过表达可损害 LSCC 细胞的活力和糖酵解，并促进其凋亡。而 miR-125b-5p 的沉默则具有相反的作用。生物信息学网站预测 MAP3K9 是 miR-125b-5p 的潜在靶基因之一。细胞实验表明，miR-125b-5p 通过直接靶向 MAP3K9 来抑制 MAP3K9 的水平。此外，在 LSCC 组织中验证了 miR-125b-5p 与 MAP3K9 之间的负相关性。MAP3K9 的过表达可减弱 miR-125b-5p 对 LSCC 细胞活力和糖酵解的抑制作用，以及 miR-125b-5p 的促凋亡作用。此外，体内实验表明，转染 miR-125b-5p 模拟物的 AMC-HN-8 细胞中的肿瘤生长受到抑制。相反，miR-125b-5p 的敲低则可在体内减少肿瘤生长。同时，体内免疫组化和 TUNEL 检测表明，miR-125b-5p 通过靶向 MAP3K9 抑制细胞增殖并促进凋亡。综上所述，miR-125b-5p 通过直接靶向 MAP3K9 在 LSCC 细胞中抑制增殖和糖酵解，促进凋亡。因此，miR-125b-5p 作为一种肿瘤抑制 miRNA，miR-125b-5p/MAP3K9 轴可能是 LSCC 治疗的有前途的候选靶点。
