生物
PI3K/AKT/mTOR通路
癌变
癌症研究
下调和上调
结直肠癌
蛋白激酶B
转移
小RNA
细胞生长
信号转导
癌症
细胞生物学
遗传学
基因
作者
Tao Jiang,Hongyu Wang,Song Hu,Yi Zhang,Jiaqi Wang,Lei Liu,Teng Xu,Ruizhi Fan,Yixin Xu,Shuai Wang,Li Shi,Zheng Li,Renhao Wang,Jun Song
标识
DOI:10.1186/s12943-021-01474-9
摘要
Accumulating studies have revealed that aberrant expression of circular RNAs (circRNAs) is widely involved in the tumorigenesis and progression of malignant cancers, including colorectal cancer (CRC). Nevertheless, the clinical significance, levels, features, biological function, and molecular mechanisms of novel circRNAs in CRC remain largely unexplored.CRC-related circRNAs were identified through bioinformatics analysis and verified in clinical specimens by qRT-PCR and in situ hybridization (ISH). Then, in vitro and in vivo experiments were performed to determine the clinical significance of, functional roles of, and clinical characteristics associated with circIL4R in CRC specimens and cells. Mechanistically, RNA pull-down, fluorescence in situ hybridization (FISH), luciferase reporter, and ubiquitination assays were performed to confirm the underlying mechanism of circIL4R.CircIL4R was upregulated in CRC cell lines and in sera and tissues from CRC patients and was positively correlated with advanced clinicopathological features and poor prognosis. Functional experiments demonstrated that circIL4R promotes CRC cell proliferation, migration, and invasion via the PI3K/AKT signaling pathway. Mechanistically, circIL4R was regulated by TFAP2C and competitively interacted with miR-761 to enhance the expression of TRIM29, thereby targeting PHLPP1 for ubiquitin-mediated degradation to activate the PI3K/AKT signaling pathway and consequently facilitate CRC progression.Our findings demonstrate that upregulation of circIL4R plays an oncogenic role in CRC progression and may serve as a promising diagnostic and prognostic biomarker for CRC detection and as a potential therapeutic target for CRC treatment.
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