Correction: Circ-HuR suppresses HuR expression and gastric cancer progression by inhibiting CNBP transactivation

Molecular Cancer(2023)

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摘要
Background Circular RNAs (circRNAs), a subclass of non-coding RNAs, play essential roles in tumorigenesis and aggressiveness. Our previous study has identified that circAGO2 drives gastric cancer progression through activating human antigen R (HuR), a protein stabilizing AU-rich element-containing mRNAs. However, the functions and underlying mechanisms of circRNAs derived from HuR in gastric cancer progression remain elusive. Methods CircRNAs derived from HuR were detected by real-time quantitative RT-PCR and validated by Sanger sequencing. Biotin-labeled RNA pull-down, mass spectrometry, RNA immunoprecipitation, RNA electrophoretic mobility shift, and in vitro binding assays were applied to identify proteins interacting with circRNA. Gene expression regulation was observed by chromatin immunoprecipitation, dual-luciferase assay, real-time quantitative RT-PCR, and western blot assays. Gain- and loss-of-function studies were performed to observe the impacts of circRNA and its protein partner on the growth, invasion, and metastasis of gastric cancer cells in vitro and in vivo . Results Circ-HuR ( hsa_circ_0049027 ) was predominantly detected in the nucleus, and was down-regulated in gastric cancer tissues and cell lines. Ectopic expression of circ-HuR suppressed the growth, invasion, and metastasis of gastric cancer cells in vitro and in vivo. Mechanistically, circ-HuR interacted with CCHC-type zinc finger nucleic acid binding protein (CNBP), and subsequently restrained its binding to HuR promoter, resulting in down-regulation of HuR and repression of tumor progression. Conclusions Circ-HuR serves as a tumor suppressor to inhibit CNBP-facilitated HuR expression and gastric cancer progression, indicating a potential therapeutic target for gastric cancer.
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关键词
Circular RNAs, Human antigen R, Gastric cancer, CCHC-type zinc finger nucleic acid binding protein
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