Department of Urology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang Province, China.
Eur Rev Med Pharmacol Sci. 2017 Oct;21(20):4566-4576.
Renal cell carcinoma (RCC) displays an increasing incidence and mortality rate worldwide in recent years. More and more evidence identified microRNAs function as positive or negative regulatory factors in many cancers, but the role of miR-21 in RCC remains unclear.
Relative expression levels of miR-21 in human RCC tissue samples and RCC-derived cell lines were measured using quantitative real-time Polymerase Chain Reaction (PCR). Clinical features were collected to further study the relationship between the miR-21 level and clinicopathologic variables. Loss- and gain- of miR-21 experiments were employed to measure the influence of miR-21 in cell proliferation, apoptosis, invasion and migration. Downstream target gene was confirmed by using luciferase and Western blotting assays.
MiR-21 significantly over-expressed in RCC tissues and cell lines than normal groups. Higher miR-21 expression level indicated larger tumor sizes, more lymph metastasis and advanced tumor node metastasis (TNM) stage. Knocking down miR-21 inhibited the cell growth, invasion and migration abilities but promoted the cell apoptosis, while over-expressing miR-21 promoted cell growth and metastasis. Furthermore, TIMP3 was confirmed as a direct target of moR-21 and inhibition of TIMP3 reserved the effect of down-regulating miR-21 in RCC cells.
Our study demonstrated miR-21 was significantly over-expressed and functioned as a tumor oncogene via TIMP3 in RCC, which could provide a potential target for RCC diagnosis and therapy.
近年来，肾细胞癌（RCC）在全球的发病率和死亡率呈上升趋势。越来越多的证据表明，microRNAs 在许多癌症中作为正或负调控因子发挥作用，但 miR-21 在 RCC 中的作用尚不清楚。
采用实时定量聚合酶链反应（PCR）检测人 RCC 组织样本和 RCC 衍生细胞系中 miR-21 的相对表达水平。收集临床特征，进一步研究 miR-21 水平与临床病理变量之间的关系。通过 miR-21 的缺失和获得实验，测量 miR-21 对细胞增殖、凋亡、侵袭和迁移的影响。通过荧光素酶和 Western blot 检测来验证下游靶基因。
miR-21 在 RCC 组织和细胞系中的表达明显高于正常组。较高的 miR-21 表达水平表明肿瘤体积较大，淋巴结转移较多，肿瘤淋巴结转移（TNM）分期较晚。敲低 miR-21 抑制细胞生长、侵袭和迁移能力，但促进细胞凋亡，而过表达 miR-21 则促进细胞生长和转移。此外，TIMP3 被证实是 miR-21 的直接靶基因，抑制 TIMP3 保留了下调 miR-21 在 RCC 细胞中的作用。
本研究表明，miR-21 在 RCC 中过度表达并通过 TIMP3 发挥肿瘤癌基因的作用，可为 RCC 的诊断和治疗提供潜在靶点。
