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上调的 miR-411-5p 水平通过靶向头颈部鳞状细胞癌中的 RYBP 促进淋巴结转移。

Upregulated miR‑411‑5p levels promote lymph node metastasis by targeting RYBP in head and neck squamous cell carcinoma.

机构信息

Department of Oral Medicine, Hospital of Stomatology, Sun Yat‑Sen University, Guangzhou, Guangdong 510055, P.R. China.

出版信息

Int J Mol Med. 2021 Apr;47(4). doi: 10.3892/ijmm.2021.4869. Epub 2021 Feb 4.

Abstract

Metastasis is the primary cause of the high mortality rates in head and neck squamous cell carcinoma (HNSCC). MicroRNA (miR)‑411‑5p has been discovered to serve an important role in cancer metastases. However, to the best of our knowledge, the association between miR‑411‑5p expression levels and HNSCC metastasis has not been thoroughly investigated. The present study aimed to research the function of miR‑411‑5p in HNSCC metastasis. The results of the present study revealed that miR‑411‑5p expression levels were upregulated in patients with HNSCC with lymph node metastasis and the upregulated expression levels of miR‑411‑5p were positively associated with the metastatic potential of HNSCC. Moreover, miR‑411‑5p promoted HNSCC cell migration, invasion and epithelial‑mesenchymal transition (EMT). The results of the dual‑luciferase reporter assays identified RING1 and YY1 binding protein (RYBP) as a functional downstream target gene for miR‑411‑5p. Therefore, whether miR‑411‑5p downregulated the expression levels of RYBP in HNSCC cells was subsequently investigated. Notably, the silencing of RYBP expression restored the stimulatory effects of miR‑411‑5p on HNSCC cell migration, invasion and EMT. In addition, the mRNA expression levels of miR‑411‑5p and RYBP were found to be inversely correlated in HNSCC samples. In conclusion, the results of the present study indicated that the miR‑411‑5p‑mediated downregulation of RYBP expression levels may exert an important role in HNSCC metastasis and may provide a novel target for the treatment of HNSCC.

摘要

转移是头颈部鳞状细胞癌 (HNSCC) 高死亡率的主要原因。已经发现 microRNA (miR)-411-5p 在癌症转移中发挥重要作用。然而,据我们所知,miR-411-5p 表达水平与 HNSCC 转移之间的关联尚未得到彻底研究。本研究旨在研究 miR-411-5p 在 HNSCC 转移中的作用。本研究的结果表明,miR-411-5p 在患有淋巴结转移的 HNSCC 患者中的表达水平上调,并且 miR-411-5p 的上调表达水平与 HNSCC 的转移潜能呈正相关。此外,miR-411-5p 促进了 HNSCC 细胞的迁移、侵袭和上皮-间充质转化 (EMT)。双荧光素酶报告基因检测结果鉴定 RING1 和 YY1 结合蛋白 (RYBP) 为 miR-411-5p 的功能下游靶基因。因此,随后研究了 miR-411-5p 是否下调了 HNSCC 细胞中 RYBP 的表达水平。值得注意的是,RYBP 表达的沉默恢复了 miR-411-5p 对 HNSCC 细胞迁移、侵袭和 EMT 的刺激作用。此外,在 HNSCC 样本中发现 miR-411-5p 和 RYBP 的 mRNA 表达水平呈负相关。综上所述,本研究结果表明,miR-411-5p 介导的 RYBP 表达水平下调可能在 HNSCC 转移中发挥重要作用,并为 HNSCC 的治疗提供了一个新的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/527d/7891818/ffcf294bf3e8/IJMM-47-04-04869-g00.jpg

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