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Circ-FAT1 Up-Regulates FOSL2 Expression by Sponging miR-619-5p to Facilitate Colorectal Cancer Progression

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Abstract

Circular RNA FAT atypical cadherin 1 (circ-FAT1) has been reported to play roles in colorectal cancer (CRC) development. Here, the purpose of this study was to investigate the function and mechanism of circ-FAT1 in CRC tumorigenesis and its potential value in the clinic. Levels of genes and proteins were examined by quantitative real-time polymerase chain reaction and Western blot. In vitro assays were conducted using cell counting kit-8 assay, 5-Ethynyl-2′-deoxyuridine assay, flow cytometry, transwell assay, and tube formation assay, respectively. The target relationship between miR-619-5p and circ-FAT1 or FOS-like antigen 2 (FOSL2) was verified by dual-luciferase reporter and RNA immunoprecipitation assays. In vivo assay was performed using a mouse subcutaneous xenograft model. Circ-FAT1 and FOSL2 were highly expressed in CRC tissues and cells. Functionally, knockdown of circ-FAT1 or FOSL2 suppressed CRC cell apoptosis, migration, invasion, and angiogenesis, but induced cell apoptosis in vitro. Mechanistically, circ-FAT1 acted as a sponge for miR-619-5p to up-regulate the expression of FOSL2, which was confirmed to be a target of miR-619-5p. A series of rescue experiments demonstrated that miR-619-5p inhibition or FOSL2 overexpression reversed the inhibitory action of circ-FAT1 silencing on CRC cell malignant phenotypes mentioned above. Pre-clinically, lentivirus-mediated circ-FAT1 knockdown inhibited the tumorigenesis of CRC xenografts in nude mice via regulating miR-619-5p and FOSL2. Circ-FAT1 knockdown repressed FOSL2 expression by sponging miR-619-5p to suppress CRC tumorigenesis, providing a potential approach for CRC therapeutics.

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Authors and Affiliations

  1. Department of Anus and Intestine Surgery, Xingtai People’s Hospital, 16 Hongxing Street, Xiangdu, Xingtai, 054000, Hebei, China

    Wanli Ma, Dongfeng Han, Bingjie Wang & Xiangsheng Wang

  2. No. 818, Xiangdu North Road, Xiangdu District, Xingtai, China

    Zhong Niu

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  1. Wanli Ma
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  2. Zhong Niu
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  3. Dongfeng Han
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  4. Bingjie Wang
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  5. Xiangsheng Wang
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Correspondence to Zhong Niu.

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Ma, W., Niu, Z., Han, D. et al. Circ-FAT1 Up-Regulates FOSL2 Expression by Sponging miR-619-5p to Facilitate Colorectal Cancer Progression. Biochem Genet 60, 1362–1379 (2022). https://doi.org/10.1007/s10528-021-10148-6

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