MiR-27b-3p has been reported to function as tumor suppressor in several tumors, including breast cancer and lung cancer. Recently, miR-27b-3p has been identified to be significantly down-regulated in esophageal cancer. However, the clinical significance and biological role of miR-27b-3p in esophageal squamous cell carcinoma (ESCC) still remain unclear. In this study, the expression levels of miR-27b-3p were significantly reduced in ESCC clinical tissues and ESCC cell lines (EC97069 and TE-1). Moreover, down-regulated expression of miR-27b-3p was associated with poor cell differentiation, TNM stage and lymph node metastasis. Specially, overexpression of miR-27b-3p significantly suppressed cell proliferation, migration and invasion in vitro using CCK-8 and transwell assays. Targetscan bioinformatics predictions and luciferase reporter assay confirmed that nuclear factor erythroid 2-related factor 2 (NFE2L2, Nrf2) was a direct target gene of miR-27b-3p. Nrf2 expression was significantly increased in ESCC tissues compared with adjacent tissues. Up-regulated expression of Nrf2 was correlated with TNM stage and lymph node metastasis. Functionally, knockdown of Nrf2 exhibited similar effects to overexpression of miR-27b-3p. Higher expression of ZO-1, E-cadherin and lower expression of N-cadherin, Vimentin and Claudin-1 were observed after miR-27b-3p overexpression of Nrf2 knockdown. Rescue experiments proved that miR-27b-3p suppressed cell proliferation, migration, invasion and epithelial to mesenchymal transition (EMT) via suppression of Nrf2. Taken together, the newly identified miR-27b-3p/Nrf2 axis might represent a new candidate therapeutic target for ESCC treatment.

中文翻译：

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MiR-27b-3p通过靶向Nrf2在食管鳞状细胞癌中发挥抑癌作用。

据报道，MiR-27b-3p在包括乳腺癌和肺癌在内的多种肿瘤中起着抑癌作用。最近，已确定miR-27b-3p在食道癌中显着下调。然而，miR-27b-3p在食管鳞状细胞癌（ESCC）中的临床意义和生物学作用仍不清楚。在这项研究中，miR-27b-3p在ESCC临床组织和ESCC细胞系（EC97069和TE-1）中的表达水平显着降低。此外，miR-27b-3p表达下调与细胞分化差，TNM分期和淋巴结转移有关。特别是，使用CCK-8和Transwell分析，miR-27b-3p的过表达在体外显着抑制了细胞增殖，迁移和侵袭。Targetscan生物信息学预测和荧光素酶报告基因测定证实，核因子红系2相关因子2（NFE2L2，Nrf2）是miR-27b-3p的直接靶基因。与邻近组织相比，ESCC组织中的Nrf2表达显着增加。Nrf2的表达上调与TNM分期和淋巴结转移有关。在功能上，敲低Nrf2表现出与miR-27b-3p过表达相似的作用。在miR-27b-3p过表达Nrf2敲低后观察到ZO-1，E-钙粘蛋白的高表达和N-钙粘蛋白，波形蛋白和Claudin-1的低表达。救援实验证明，miR-27b-3p通过抑制Nrf2来抑制细胞增殖，迁移，侵袭和上皮向间质转化（EMT）。在一起