Abstract
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.
Highlights
Clear cell renal cell carcinoma, the most common renal cell carcinoma (RCC) [1], characterizes with high metastasis [2, 3]
Figure 1: circ-ITCH inhibits Clear cell renal cell carcinoma (ccRCC) cell migration and invasion. (a, b) The expression of circ-ITCH in ccRCC tissues and cells by qT-PCR. (c, d) Transwell assay determines the role of circ-ITCH in migration and invasion of OSRC-2 and SW839 cells. (e) Wound healing detects the effect of circ-ITCH downregulation on the migration abilities of OSRC-2 and SW839 cells. (f) The expressions of E-cadherin and N-cadherin in OSRC-2 and SW839 cells transfected with OE-circ-ITCH
We firstly found that circ-ITCH levels were reduced in ccRCC tissues and ccRCC cell lines, which was similar with the fact that it existed the abnormal expression of circ-ITCH in other cancers [32]
Summary
Clear cell renal cell carcinoma (ccRCC), the most common renal cell carcinoma (RCC) [1], characterizes with high metastasis [2, 3]. The 5-year survival rate of RCC patients who are diagnosed at metastatic stage only have 12% [4] At present, it lacks targeted and effective management marker for ccRCC metastasis in clinic. It is necessary for RCC to find new circRNAs target Among these circRNAs, circular RNA ITCH (circ-ITCH) acts as a tumor suppressor in the occurrence of several tumors, such as hepatocellular carcinoma [22], ovarian cancer [23], oral squamous cell carcinoma [24], cervical cancer [25], osteosarcoma [26], and Journal of Immunology Research prostate cancer [27]. Programmed cell death 4 (PDCD4), a tumor suppressor, is firstly clarified as a gene that induces apoptosis in murine cell line [28] It is frequently downregulated in cancers and inhibits tumor promotion, development, proliferation, invasion, and metastasis [29, 30]. Circ-ITCH might become a novel target to inhibit ccRCC metastasis
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