Department of Urology, Chinese PLA General Hospital, Beijing, China.
Department of Urology, Hainan Branch of Chinese PLA General Hospital, Sanya, China.
J Cell Physiol. 2019 Mar;234(3):2581-2592. doi: 10.1002/jcp.27020. Epub 2018 Sep 19.
Renal cell carcinoma (RCC) is the most common malignancy involving the kidneys and a major cause of cancer mortality. The involvement of microRNA (miRNA) expression in the tumorigenesis and progression of RCC has been previously highlighted. Therefore, we conducted this study to investigate whether microRNA-363 (miR-363) affects the development of RCC via the Janus tyrosine kinases (JAK2)-signal transducers and activators of transcription (STAT) axis by targeting the growth hormone receptor (GHR), by observing the changes that occurred in the RCC and the normal adjacent tissues of patients with RCC. RCC cells were transfected with a series of miR-363 mimic, miR-363 inhibitor, or small interfering RNA against GHR to determine the influence of miR-363 on the expression of GHR and JAK2-STAT3 axis-related genes with the use of reverse transcription quantitative polymerase chain reaction and Western blot analysis. The angiogenesis, viability, invasion, and migration of cells were evaluated by means of in vitro angiogenesis, 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT), wound-healing, and Transwell assays. The results revealed reduced miR-363 expression and elevated GHR expression in RCC. It was also found that miR-363 altered the activation of the JAK2-STAT3 axis through the inhibition of GHR. Cells treated with the miR-363 inhibitor presented with increased capillary vessels, cell viability, invasion, and migration, whereas it was on the contrary in the RCC cells with overexpressed miR-363. These results implicated that the overexpression of miR-363 could specifically bind to GHR to downregulate the expression of GHR, which, in turn, inactivates the JAK2-STAT3 axis, thereby influencing the angiogenesis, cell invasion, and migration abilities in RCC.
肾细胞癌 (RCC) 是最常见的肾脏恶性肿瘤，也是癌症死亡的主要原因。miRNA 表达在 RCC 的发生和发展中起着重要作用。因此，我们通过观察 RCC 患者肿瘤组织和正常邻近组织中发生的变化，研究了 microRNA-363 (miR-363) 是否通过靶向生长激素受体 (GHR) 影响 RCC 的发生发展，进而影响 RCC 的发生发展。JAK2-STAT 轴。RCC 细胞转染了一系列 miR-363 模拟物、miR-363 抑制剂或针对 GHR 的小干扰 RNA，以确定 miR-363 对 GHR 和 JAK2-STAT3 轴相关基因表达的影响。采用逆转录定量聚合酶链反应和 Western blot 分析。通过体外血管生成、3-(4,5)-二甲基噻唑 (-z-y1)-3,5-二苯基四氮唑溴盐 (MTT)、划痕愈合和 Transwell 分析评估细胞的血管生成、活力、侵袭和迁移能力。结果显示，RCC 中 miR-363 表达降低，GHR 表达升高。还发现 miR-363 通过抑制 GHR 改变了 JAK2-STAT3 轴的激活。用 miR-363 抑制剂处理的细胞中毛细血管增多，细胞活力、侵袭和迁移增加，而在过表达 miR-363 的 RCC 细胞中则相反。这些结果表明，miR-363 的过表达可以特异性结合 GHR 下调 GHR 的表达，进而使 JAK2-STAT3 轴失活，从而影响 RCC 的血管生成、细胞侵袭和迁移能力。
