Background:

Although renal cell carcinoma remains one of the most malignant cancers, our understanding of progression and recurrence of this disease is limited. The present study explored the precise role of miR-155-5p in renal cancer metastasis.

Methods:

The expression of miR-155-5p in renal carcinoma clinical tissues and cells was determined using quantitative real time-polymerase chain reaction. The role of miR-155-5p on tumor cell growth were examined using CCK-8 and colony formation assays. Transwell assay was utilized to identify the role of miR-155-5p on the invasion and migration of renal cancer cells. Markers of epithelial-mesenchymal transition were determined using western blot. The in vivo effects of miR-155-5p on renal cancer cell growth, apoptosis, and metastasis were explored using xenograft mice. Luciferase reporter assay was performed to identify the potential target of miR-155-5p.

Results:

Levels of miR-155-5p were significantly elevated in renal cancer tissues and cell lines. Suppression of miR-155-5p decreased the growth, colony formation, migration, and invasiveness of renal cancer cells. In contrast, overexpression of miR-155-5p led to opposite effects on renal cancer cells. Mechanically, the apoptosis-inducing factor was identified as the target of miR-155-5p. Interference of miR-155-5p significantly increased mRNA and protein expression of the apoptosis-inducing factor, whereas overexpression of miR-155-5p remarkably suppressed the apoptosis-inducing factor levels in renal cancer cells. The xenograft model identified that suppression of miR-155-5p restrained tumor growth and promoted apoptosis, whereas overexpression of miR-155-5p decreased apoptosis and accelerated tumor growth. Moreover, the number of lung metastasis nodules were decreased following injection with anti-miR-155-5p transfected cells, whereas the nodules were remarkably increased after overexpression of miR-155-5p. In addition, in vitro and in vivo assays both confirmed that suppression of miR-155-5p increased the expression of E-cadherin and decreased levels of N-cadherin and Snail, whereas overexpression of miR-155-5p accelerated epithelial–mesenchymal transition progression in renal cancer cells.

Conclusion:

These findings demonstrate that miR-155-5p enhances metastasis and epithelial–mesenchymal transition by targeting the apoptosis-inducing factor, suggesting that miR-155-5p represents a novel therapeutic target for renal cancer.

中文翻译：

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MiR-155-5p通过靶向凋亡诱导因子促进肾细胞癌的转移和上皮-间质转化

背景：

尽管肾细胞癌仍然是最恶性的癌症之一，但我们对这种疾病的进展和复发的了解是有限的。本研究探讨了 miR-155-5p 在肾癌转移中的确切作用。

方法：

使用定量实时聚合酶链反应测定肾癌临床组织和细胞中 miR-155-5p 的表达。使用 CCK-8 和集落形成测定检查 miR-155-5p 对肿瘤细胞生长的作用。Transwell检测用于鉴定miR-155-5p对肾癌细胞侵袭和迁移的作用。使用蛋白质印迹测定上皮-间质转化的标志物。使用异种移植小鼠探索了 miR-155-5p 对肾癌细胞生长、凋亡和转移的体内影响。进行荧光素酶报告基因测定以鉴定 miR-155-5p 的潜在靶标。

结果：

肾癌组织和细胞系中 miR-155-5p 的水平显着升高。抑制 miR-155-5p 会降低肾癌细胞的生长、集落形成、迁移和侵袭性。相比之下，miR-155-5p 的过表达对肾癌细胞产生了相反的影响。机械地，凋亡诱导因子被确定为 miR-155-5p 的靶标。miR-155-5p的干扰显着增加了凋亡诱导因子的mRNA和蛋白表达，而miR-155-5p的过表达显着抑制了肾癌细胞中凋亡诱导因子的水平。异种移植模型发现，抑制 miR-155-5p 会抑制肿瘤生长并促进细胞凋亡，而过表达 miR-155-5p 会减少细胞凋亡并加速肿瘤生长。而且，注射抗miR-155-5p转染细胞后肺转移结节数量减少，而miR-155-5p过表达后肺转移结节数量显着增加。此外，体外和体内试验均证实抑制 miR-155-5p 会增加 E-cadherin 的表达并降低 N-cadherin 和 Snail 的水平，而 miR-155-5p 的过表达会加速上皮-间质转化进程在肾癌细胞中。

结论：

这些发现表明，miR-155-5p 通过靶向凋亡诱导因子来增强转移和上皮-间质转化，这表明 miR-155-5p 代表了肾癌的新治疗靶点。