MicroRNAs (miRNAs) are short single-stranded RNAs, measuring 21 to 23 nucleotides in length and regulate gene expression at the post-transcriptional level through mRNA destabilization or repressing protein synthesis. Dysregulation of miRNAs can lead to tumorigenesis through changes in regulation of key cellular processes such as cell proliferation, cell survival, and apoptosis. miR-125a-5p has been implicated as a tumor suppressor miRNA in malignancies such as non-small cell lung cancer and colon cancer. However, the role of miR-125a-5p has not been fully investigated in head and neck squamous cell carcinoma (HNSCC). We performed microRNA microarray profiling of HNSCC tumor samples obtained from a prospective clinical trial evaluating the role of postoperative radiotherapy in head and neck cancer. We also mined through The Cancer Genome Atlas to evaluate expression and survival data. Biological experiments, including cell proliferation, flow cytometry, cell migration and invasion, clonogenic survival, and fluorescent microscopy, were conducted using HN5 and UM-SCC-22B cell lines. miR-125a-5p downregulation was associated with recurrent disease in a panel of high-risk HNSCC and then confirmed poor survival associated with low expression in HNSCC via the Cancer Genome Atlas, suggesting that miR-125a-5p acts as a tumor suppressor miRNA. We then demonstrated that miR-125a-5p regulates cell proliferation through cell cycle regulation at the G₁/S transition. We also show that miR-125a-5p can alter cell migration and modulate sensitivity to ionizing radiation. Finally, we identified putative mRNA targets of miR-125a-5p, including ERBB2, EIF4EBP1, and TXNRD1, which support the tumor suppressive mechanism of miR-125a-5p. Functional validation of ERBB2 suggests that miR-125a-5p affects cell proliferation and sensitivity to ionizing radiation, in part, through ERBB2. Our data suggests that miR-125a-5p acts as a tumor suppressor miRNA, has potential as a diagnostic tool and may be a potential therapeutic target for the management and treatment of squamous cell carcinoma of the head and neck.

MicroRNA（miRNA）是短的单链RNA，长度为21至23个核苷酸，并通过mRNA不稳定或抑制蛋白合成在转录后水平调控基因表达。miRNA的失调可通过改变关键细胞过程（例如细胞增殖，细胞存活和凋亡）的调控而导致肿瘤发生。在非小细胞肺癌和结肠癌等恶性肿瘤中，miR-125a-5p被认为是一种抑癌miRNA。但是，miR-125a-5p在头颈部鳞状细胞癌（HNSCC）中的作用尚未得到充分研究。我们对HNSCC肿瘤样本进行了microRNA芯片分析，该样本来自一项前瞻性临床试验，评估了术后放疗在头颈癌中的作用。我们还通过《癌症基因组图集》进行了挖掘，以评估表达和生存数据。使用HN5和UM-SCC-22B细胞系进行了生物学实验，包括细胞增殖，流式细胞术，细胞迁移和侵袭，克隆形成存活和荧光显微镜检查。miR-125a-5p的下调与一组高风险HNSCC中的复发性疾病相关，然后证实了与HNSCC中低表达相关的不良生存通过癌症基因组图谱，表明miR-125a-5p可作为抑癌miRNA。然后，我们证明了miR-125a-5p通过在G ₁ / S过渡时的细胞周期调控来调控细胞增殖。我们还显示，miR-125a-5p可以改变细胞迁移并调节对电离辐射的敏感性。最后，我们确定了miR-125a-5p的假定mRNA靶标，包括ERBB2，EIF4EBP1和TXNRD1，它支持miR-125a-5p的肿瘤抑制机制。ERBB2的功能验证表明，miR-125a-5p部分地通过ERBB2影响细胞增殖和对电离辐射的敏感性。我们的数据表明，miR-125a-5p可用作抑癌miRNA，具有作为诊断工具的潜力，并且可能是头颈部鳞状细胞癌的治疗和治疗的潜在治疗靶标。