Mounting evidence has indicated that aberrantly expressed microRNAs (miRNAs) play key roles in tumorigenesis, including in head and neck squamous cell carcinoma (HNSCC). Previous studies have shown that miR‐335‐5p can serve as a tumor suppressor or an oncogene in cancer. However, the clinical importance and biological effects of miR‐335‐5p in HNSCC have not been determined. Here, we investigated the expression pattern, functional role, and mechanisms of miR‐335‐5p in HNSCC. We showed a decreased expression of miR‐335‐5p in HNSCC samples from the TCGA and GEO databases. Consistently, we detected a downregulation of miR‐335‐5p in HNSCC cell lines and patient tissues. The expression of miR‐335‐5p was inversely correlated with advanced clinical TNM stage and lymph node metastasis in HNSCC patients. miR‐335‐5p overexpression inhibited HNSCC cell proliferation and induced apoptosis, while miR‐335‐5p inhibition had the opposite effects. miR‐335‐5p overexpression suppressed tumor growth in mice. Bioinformatic analyses and functional assays identified MAP3K2 as a target of miR‐335‐5p, and we showed that miR‐335‐5p downregulated mitogen‐activated protein kinase kinase kinase 2 (MAP3K2) expression in HNSCC cells. We found an inverse association between MAP3K2 and miR‐335‐5p expression in 38 pairs of HNSCC tissues. Furthermore, the effect of miR‐335‐5p overexpression on growth and metastasis as well as cell apoptosis in HNSCC cells could be partially rescued by MAP3K2 expression. Collectively, our data show that miR‐335‐5p inhibits the development of HNSCC by regulating MAP3K2 expression. Thus, these findings offer novel insights into a potential therapeutic strategy for HNSCC patients.

中文翻译：

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MiR-335-5p通过靶向MAP3K2抑制头颈部鳞状细胞癌的发展

越来越多的证据表明，异常表达的microRNA（miRNA）在肿瘤发生中起关键作用，包括在头颈部鳞状细胞癌（HNSCC）中。先前的研究表明，miR-335-5p可以作为癌症的抑癌药或癌基因。但是，尚未确定miR-335-5p在HNSCC中的临床重要性和生物学作用。在这里，我们研究了miR-335-5p在HNSCC中的表达模式，功能作用和机制。我们在TCGA和GEO数据库的HNSCC样本中显示了miR-335-5p的表达降低。一致地，我们在HNSCC细胞系和患者组织中检测到miR-335-5p的下调。HNSCC患者中miR-335-5p的表达与晚期TNM分期和淋巴结转移呈负相关。miR-335-5p的过表达抑制HNSCC细胞增殖并诱导凋亡，而miR-335-5p的抑制作用却相反。miR-335-5p过表达抑制了小鼠的肿瘤生长。确定生物信息学分析和功能测定MAP3K2作为miR-335-5p的靶标，我们发现miR-335-5p下调了HNSCC细胞中促分裂原活化的蛋白激酶激酶2（MAP3K2）的表达。我们在38对HNSCC组织中发现MAP3K2与miR-335-5p表达之间呈负相关。此外，MAP3K2表达可以部分挽救miR-335-5p过表达对HNSCC细胞生长和转移以及细胞凋亡的影响。总体而言，我们的数据表明，miR-335-5p通过调节MAP3K2表达来抑制HNSCC的发展。因此，这些发现为HNSCC患者的潜在治疗策略提供了新颖的见解。