MicroRNA-485-5p suppresses the progression of esophageal squamous cell carcinoma by targeting flotillin-1 and inhibits the epithelial-mesenchymal transition
MicroRNA-485-5p suppresses the progression of esophageal squamous cell carcinoma by targeting flotillin-1 and inhibits the epithelial-mesenchymal transition
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DOI：
10.3892/or.2021.8044
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发表时间：
2021-04
期刊：
影响因子：
4.2
通讯作者：
Riyang Zhao;Yanan Shan;Xinliang Zhou;Cong Zhang;Ruinian Zhao;Lianmei Zhao;B. Shan
中科院分区：
文献类型：
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作者：
Riyang Zhao;Yanan Shan;Xinliang Zhou;Cong Zhang;Ruinian Zhao;Lianmei Zhao;B. Shan
由于食管鳞状细胞癌（ESCC）是亚洲最常见的癌症之一，因此揭示其支持其发展和进展的潜在分子机制至关重要。已有多篇文章报道microRNA（miR）-485-5p抑制多种癌症类型（如肺癌、胃癌和乳腺癌）中的恶性表型，但据我们所知，直到本研究，其在ESCC中的功能尚未被深入研究。探讨miR-485- 5 p在食管鳞癌中的调控作用及其机制具有重要意义。总之，本研究确定miR-485- 5 p在ESCC组织中的表达显著低于正常组织。miR-485- 5 p表达的降低与肿瘤大小较大、组织学和分期较差相关。miR-485- 5 p在Eca 109和TE-1细胞中的表达相对较高，但在KYSE 30中的表达相对较低。miR-485- 5 p的过表达抑制了体外细胞的增殖、迁移和侵袭，而miR-485- 5 p的敲低则相反。Flotillin-1（FLOT-1）可以促进各种癌症类型的恶性表型。本研究发现，在食管鳞癌组织中，FLOT-1的蛋白表达与miR-485- 5 p的表达呈负相关。进一步的实验表明，miR-485- 5 p直接靶向FLOT-1的3′-非翻译区。miR-485- 5 p的过表达显著抑制了FLOT-1的mRNA和蛋白表达水平，而敲低则具有相反的效果。此外，miR-485- 5 p的过表达在mRNA和蛋白水平上抑制了上皮间质转移（EMT）相关因子。同时，在体内也能抑制食管鳞癌的生长，抑制EMT的发生。总之，发现miR-485- 5 p是ESCC的抑制剂，并且可能具有作为ESCC治疗的新靶点候选者的潜力。
As esophageal squamous cell carcinoma (ESCC) is one of the most frequently diagnosed cancers in Asia, it is crucial to uncover its underlying molecular mechanisms that support its development and progression. Several articles have reported that microRNA (miR)-485-5p inhibits the malignant phenotype in a number of cancer types, such as lung, gastric and breast cancer, but to the best of our knowledge, its function in ESCC has not been studied in depth until the present study. It is of great significance to probe the regulatory action and underlying mechanism of miR-485-5p in ESCC. In brief, this study identified that miR-485-5p expression in ESCC tissues was significantly lower than that in normal tissues. The decrease in miR-485-5p expression was associated with a larger tumour size and poor histology and stage. The expression of miR-485-5p was relatively high in Eca 109 and TE-1 cells, but relatively low in KYSE 30. The overexpression of miR-485-5p inhibited cell proliferation, migration and invasion in vitro, whereas miR-485-5p knockdown did the opposite. Flotillin-1 (FLOT-1) can facilitate the malignant phenotype in various cancer types. The present study found that in ESCC tissue, the protein expression of FLOT-1 was negatively correlated with miR-485-5p expression. Further experiments showed that miR-485-5p directly targeted the 3′-untranslated region of FLOT-1. The overexpression of miR-485-5p significantly suppressed the mRNA and protein expression levels of FLOT-1, whereas knockdown had the reverse effects. Furthermore, overexpression of miR-485-5p restrained epithelial-mesenchymal metastasis (EMT)-related factors at both the mRNA and protein levels. At the same time, it also inhibited the growth of ESCC and restrained the EMT in vivo. In summary, miR-485-5p was found to be an inhibitor of ESCC and may have potential as a novel target candidate for ESCC treatment.