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miR-125b-5p 的升高与喉鳞状细胞癌的预后改善有关,并通过靶向 MAP3K9 抑制肿瘤的恶性表型和糖代谢紊乱。

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.

机构信息

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.

出版信息

Neoplasma. 2022 May;69(3):550-559. doi: 10.4149/neo_2022_211027N1532. Epub 2022 Feb 22.

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. 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.

摘要

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。

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