%0 Journal Article
%T Aberrant expression of circular RNA DHPR facilitates tumor growth and metastasis by regulating the RASGEF1B/RAS/MAPK axis in hepatocellular carcinoma.
%A Guo Z
%A Xie Q
%A Wu Y
%A Mo H
%A Zhang J
%A He G
%A Li Z
%A Gan L
%A Feng L
%A Li T
%A Wang Y
%A Fu Y
%A Cai L
%A Li S
%A Yu C
%A Gao Y
%A Pan M
%A Fu S
%J Cell Oncol (Dordr)
%V 46
%N 5
%D 2023 Oct 26
%M 37099250
%F 7.051
%R 10.1007/s13402-023-00814-9
%X <B>BACKGROUND: </B>Circular RNAs (circRNAs) are noncoding RNAs. Accumulating evidence suggests that circRNAs play a critical role in human biological processes, especially tumorigenesis, and development. However, the exact mechanisms of action of circRNAs in hepatocellular carcinoma (HCC) remain unclear.<BR><B>METHODS: </B>Bioinformatic tools and RT-qPCR were used to identify the role of circDHPR, a circRNA derived from the dihydropteridine reductase (DHPR) locus, in HCC and para-carcinoma tissues. Kaplan-Meier analysis and the Cox proportional hazard model were used to analyze the correlation between circDHPR expression and patient prognosis. Lentiviral vectors were used to establish stable circDHPR-overexpressing cells. In vitro and in vivo studies have shown that tumor proliferation and metastasis are affected by circDHPR. Mechanistic assays, including Western blotting, immunohistochemistry, dual-luciferase reporter assays, fluorescence in situ hybridization, and RNA immunoprecipitation, have demonstrated the molecular mechanism underlying circDHPR.<BR><B>RESULTS: </B>CircDHPR was downregulated in HCC, and low circDHPR expression was associated with poor overall survival and disease-free survival rates. CircDHPR overexpression inhibits tumor growth and metastasis in vitro and in vivo. Further systematic studies revealed that circDHPR binds to miR-3194-5p, an upstream regulator of RASGEF1B. This endogenous competition suppresses the silencing effect of miR-3194-5p. We confirmed that circDHPR overexpression inhibited HCC growth and metastasis by sponging miR-3194-5p to upregulate the expression of RASGEF1B, which is regarded as a suppressor of the Ras/MAPK signaling pathway.<BR><B>CONCLUSIONS: </B>Aberrant circDHPR expression leads to uncontrolled cell proliferation, tumorigenesis, and metastasis. CircDHPR may serve as a biomarker and therapeutic target for HCC.