Department of Urology Surgery, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, 610072 Sichuan Province, China.
Department of Pharmacy, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, 610072 Sichuan Province, China.
J Immunol Res. 2021 Apr 20;2021:5524344. doi: 10.1155/2021/5524344. eCollection 2021.
High metastasis of clear cell renal cell carcinoma (ccRCC) significantly influenced survival rate of ccRCC patients. Here, we intended to investigate the impacts of circular RNA ITCH (circ-ITCH) on the metastasis of ccRCC. The expression of circ-ITCH in ccRCC tissues and cells was evaluated utilizing qRT-PCR. Transwell assay and wound healing were applied to investigate migration and invasion of ccRCC cells. Target gene prediction and screening and luciferase reporter gene assays were utilized to assess downstream target genes of circ-ITCH. Western blot was utilized to detect metastasis-related protein expression. A xenograft tumor model was established to evaluate the role of circ-ITCH in vivo. Results showed that circ-ITCH was low expressed in ccRCC tissues and cells. Downregulation circ-ITCH promoted cell migration, but overexpressing circ-ITCH inhibited cell migration and invasion in OSRC-2 and SW839 cells. Mechanism investigations claimed that circ-ITCH exerted its metastasis-inhibitory activity via sponging miR-106b-5p and regulating the expression of PDCD4. Conclusively, circ-ITCH suppresses ccRCC metastasis by enforcing PDCD4 expression through binding miR-106b-5p. circ-ITCH may function as a novel diagnostic target to suppress ccRCC metastasis.
高转移性透明细胞肾细胞癌（ccRCC）显著影响 ccRCC 患者的生存率。在这里，我们旨在研究环状 RNA ITCH（circ-ITCH）对 ccRCC 转移的影响。利用 qRT-PCR 评估 circ-ITCH 在 ccRCC 组织和细胞中的表达。通过 Transwell 分析和划痕愈合实验来研究 ccRCC 细胞的迁移和侵袭。利用靶基因预测和筛选以及荧光素酶报告基因实验来评估 circ-ITCH 的下游靶基因。利用 Western blot 检测转移相关蛋白的表达。建立异种移植肿瘤模型来评估 circ-ITCH 在体内的作用。结果表明，circ-ITCH 在 ccRCC 组织和细胞中低表达。下调 circ-ITCH 促进了 OSRC-2 和 SW839 细胞的迁移，但过表达 circ-ITCH 抑制了细胞的迁移和侵袭。机制研究表明，circ-ITCH 通过海绵吸附 miR-106b-5p 并调节 PDCD4 的表达发挥其抑制转移的活性。结论，circ-ITCH 通过结合 miR-106b-5p 抑制 PDCD4 的表达从而抑制 ccRCC 的转移。circ-ITCH 可能作为一种新型的诊断靶点来抑制 ccRCC 的转移。
