Department of Ear, Nose and Throat, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
Int J Oncol. 2019 Apr;54(4):1245-1255. doi: 10.3892/ijo.2019.4711. Epub 2019 Feb 4.
Hypopharyngeal carcinoma (HPC) is an aggressive malignancy with the worst prognosis among all head and neck cancers. MicroRNAs (miRNAs) are involved in the development of many human cancers, and may function as oncogenes or tumor suppressors. The present study aimed to evaluate the effects of miRNA (miR)‑194‑5p on the proliferation and invasion of HPC cells and to identify the potential regulatory mechanism. First, miR‑194‑5p and Smad ubiquitin regulatory factor 1 (SMURF1) expression levels were examined in HPC tissues. Subsequently, to explore the effects of miR‑194‑5p on SMURF1, a dual‑luciferase reporter gene assay was performed to verify the target relationship. To define the role of miR‑194‑5p in HPC progression, miR‑194‑5p upregulation and depletion were used to evaluate its effects on cell viability, invasion and migration. SMURF1 silencing and rapamycin [an inhibitor of the mammalian target of rapamycin (mTOR) signaling pathway] treatment were also used to analyze the regulatory mechanism in HPC. Finally, tumor growth was assessed in xenografted tumors in nude mice. SMURF1 was demonstrated to be highly expressed, whereas miR‑194‑5p was poorly expressed in HPC tissues; SMURF1 was identified as a target gene of miR‑194‑5p. FaDu hypopharyngeal squamous cell carcinoma cells treated with miR‑194‑5p mimics exhibited decreased viability, invasion and migration. The results indicated that miR‑194‑5p may inactivate the mTOR signaling pathway by targeting SMURF1. In addition, the in vivo experiments further verified these regulatory effects. These data suggested that miR‑194‑5p‑targeted SMURF1 inhibition may be involved in the disruption of HPC progression through the repression of the mTOR signaling pathway.
下咽癌（HPC）是一种侵袭性恶性肿瘤，其预后在所有头颈部癌症中最差。微小 RNA（miRNA）参与了许多人类癌症的发生，可能作为癌基因或肿瘤抑制因子发挥作用。本研究旨在评估 miRNA（miR）-194-5p 对 HPC 细胞增殖和侵袭的影响，并确定潜在的调控机制。首先，检测了 HPC 组织中 miR-194-5p 和 Smad 泛素调节因子 1（SMURF1）的表达水平。随后，为了探讨 miR-194-5p 对 SMURF1 的影响，进行了双荧光素酶报告基因检测以验证靶关系。为了明确 miR-194-5p 在 HPC 进展中的作用，使用 miR-194-5p 上调和下调来评估其对细胞活力、侵袭和迁移的影响。还使用 SMURF1 沉默和雷帕霉素[哺乳动物雷帕霉素靶蛋白（mTOR）信号通路的抑制剂]处理来分析 HPC 中的调节机制。最后，在裸鼠的异种移植肿瘤中评估了肿瘤生长情况。结果表明，SMURF1 在 HPC 组织中高表达，而 miR-194-5p 低表达；SMURF1 被鉴定为 miR-194-5p 的靶基因。转染 miR-194-5p 模拟物的 FaDu 下咽鳞状细胞癌细胞的活力、侵袭和迁移能力降低。这些结果表明，miR-194-5p 可能通过靶向 SMURF1 使 mTOR 信号通路失活。此外，体内实验进一步验证了这些调节作用。这些数据表明，miR-194-5p 靶向抑制 SMURF1 可能通过抑制 mTOR 信号通路参与破坏 HPC 的进展。
