Abstract
Circular RNAs (circRNAs) are a type of covalently closed circular-formed RNAs and play crucial roles in the oncogenesis and progression of various human cancers. Here we identified a novel circRNA, circPPP6R3, to be highly expressed both in clear cell renal cell carcinoma (ccRCC) tissues and cell lines based on analyzing high-throughput sequencing data and qRT-PCR analysis. Highly expressed circPPP6R3 was positively correlated with higher histological grade, T stage, and M stage as well as advanced clinical stage of ccRCC patients. Functionally, knockdown of circPPP6R3 attenuated the proliferation, migration, and invasion of ccRCC cells whereas overexpression had the reverse effects. Mechanistically, the biotin-labeled pull-down assay and dual-luciferase reporter assay revealed that circPPP6R3 directly interacted with miR-1238-3p. miR-1238-3p inhibitors had a rescue effect on the proliferative and metastatic capacities by knockdown of circPPP6R3. Moreover, RNA-sequencing analysis and dual-luciferase reporter assay indicated that circPPP6R3 upregulated CD44, a cell-surface glycoprotein contributed to the cell adhesion and metastasis, via sponging to miR-1238-3p. Further investigation revealed that MMP9 and Vimentin were regulated by CD44 in ccRCC. Our study thus provided evidence that the regulatory network involving circPPP6R3/miR-1238-3p/CD44 axis might provide promising biomarkers as well as a therapeutic approach for ccRCC.
Highlights
Renal cell carcinoma (RCC) is one of the most common malignant tumors of the urinary system
IHC was in clear cell RCC (ccRCC) cell lines, the results demonstrated that circPPP6R3 was subsequently performed to stain Ki67 in the tumor slides, and slightly downregulated after 24 h while PPP6R3 mRNA was the results showed that Ki67 was upregulated in the circPPP6R3
In conclusion, our investigations demonstrated that circPPP6R3 was highly expressed in ccRCC tissues and was associated with inferior clinical characteristics of ccRCC patients
Summary
Renal cell carcinoma (RCC) is one of the most common malignant tumors of the urinary system. CircRNAs have already been identified [18,19,20], the vital roles of disease-free survival rates compared with low circPPP6R3 exprescircRNAs in the progression of RCC still need to be elucidated sion (p < 0.05, Fig. 1I). Chip analysis from the GEO database [21] as well as the differentially expressed circRNAs between ccRCC cell line and Knockdown of circPPP6R3 inhibited the proliferation, renal tubular epithelial cell line in Cancer-Specific circRNA network migration, and invasion of ccRCC cells database [22]. The migratory and comprising of four paired ccRCC tissues and the adjacent normal invasive abilities were reduced after silencing the expression of renal tissues, along with the results of the differentially expressed circPPP6R3 in ccRCC cells, detected by the transwell assay, circRNAs between the ccRCC cell line Caki-2 and HK-2, the renal invasion assay, and wound-healing assay (Fig. 2E, F). 139 circRNAs (fold change ≥2.0 and p < 0.05) were upregulated Overexpression of circPPP6R3 promoted the tumorigenesis both in ccRCC tissues and cell lines, a clustered heatmap was and metastasis of ccRCC cells in vivo employed to show the top 100 upregulated circRNAs
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
