miR-424-5p Promotes Proliferation, Migration and Invasion of Laryngeal Squamous Cell Carcinoma
miR-424-5p Promotes Proliferation, Migration and Invasion of Laryngeal Squamous Cell Carcinoma
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miR-424-5p促进喉鳞状细胞癌的增殖、迁移和侵袭
DOI：
10.2147/ott.s224325
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发表时间：
2019-01-01
影响因子：
4
通讯作者：
Wu, Yongyan
中科院分区：
文献类型：
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作者：
Li, Yujun;Liu, Jie;Wu, Yongyan
背景最近的研究表明，miR-424-5p 调节多种癌症类型的恶性行为。然而，miR-424-5p在喉鳞状细胞癌（LSCC）中的表达和功能尚不清楚。目的 本研究旨在评估miR-424-5p水平与LSCC临床特征的关系，并探讨miR-424-5p对LSCC进展的影响和潜在机制。方法采用定量PCR（qPCR）技术检测106例LSCC患者及配对癌旁正常切缘（ANM）组织中miR-424-5p的表达情况，并分析其临床意义。预测miR-424-5p的靶基因，然后进行功能注释。通过对 LSCC 细胞系进行分子和细胞实验，并使用流式细胞术进行细胞周期分析，研究了 miR-424-5p 在 LSCC 中的功能作用。此外，通过 qPCR、蛋白质印迹分析和荧光素酶报告基因测定验证了 miR-424-5p 对预测靶基因细胞粘附分子 1 (CADM1) 的调节。结果 与 ANM 组织相比，miR-424-5p 在 LSCC 组织中表达上调。高miR-424-5p水平与低分化、晚期肿瘤分期和颈部淋巴结转移显着相关。生物信息学分析显示，miR-424-5p靶基因主要富集于细胞周期、细胞分裂、细胞迁移负调控等生物过程，并参与多个癌症相关通路。 miR-424-5p的过表达促进LSCC细胞的增殖、迁移、侵袭和粘附，并影响细胞周期进程。此外，CADM1 是 LSCC 细胞中 miR-424-5p 的直接靶标。结论 miR-424-5p作为癌基因促进LSCC侵袭性进展，CADM1是LSCC细胞中miR-424-5p的直接下游靶标。 miR-424-5p可能是LSCC的潜在治疗靶点。
Background Recent studies revealed that miR-424-5p regulates the malignant behavior of multiple cancer types. However, the expression and function of miR-424-5p in laryngeal squamous cell carcinoma (LSCC) is unclear. Purpose This study aimed to evaluate the association of miR-424-5p level with clinical features of LSCC and investigate the effect and potential mechanism of miR-424-5p on LSCC progression. Methods The expression of miR-424-5p in LSCC and paired adjacent normal margin (ANM) tissues from 106 patients with LSCC were analyzed by quantitative PCR (qPCR), and clinical significance was analyzed. Target genes of miR-424-5p were predicted, followed by functional annotation. The functional role of miR-424-5p in LSCC was investigated by molecular and cellular experiments with LSCC cell lines, with flow cytometry used for cell cycle analysis. In addition, miR-424-5p regulation of the predicted target gene cell adhesion molecule 1 (CADM1) was validated by qPCR, Western blot analysis and luciferase reporter assay. Results miR-424-5p was upregulated in LSCC versus ANM tissues. High miR-424-5p level was significantly associated with poor differentiation, advanced tumor stage and cervical lymph node metastasis. Bioinformatics analysis showed that miR-424-5p target genes are mainly enriched in biological processes of the cell cycle, cell division, and negative regulation of cell migration, and were involved in multiple cancer-related pathways. Overexpression of miR-424-5p promoted proliferation, migration, invasion, and adhesion of LSCC cells and affected the cell cycle progression. Additionally, CADM1 was a direct target of miR-424-5p in LSCC cells. Conclusion miR-424-5p functions as an oncogene to promote the aggressive progression of LSCC, and CADM1 is a direct downstream target of miR-424-5p in LSCC cells. miR-424-5p may be a potential therapeutic target in LSCC.