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Circ-TFF1 Facilitates Breast Cancer Development via Regulation of miR-338-3p/FGFR1 Axis

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Abstract

Some circular RNAs (circRNAs) have been verified to act as essential regulators in the progression of breast cancer (BC). We aimed to investigate the role of circRNA trefoil factor 1 (circ-TFF1) in BC progression. The expression of circ-TFF1, microRNA-338-3p (miR-338-3p) and fibroblast growth factor receptor 1 (FGFR1) mRNA was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was evaluated by methylthiazolyldiphenyl-tetrazolium bromide (MTT), colony formation, and 5-Ethynyl-2′-deoxyuridine (EDU) assays. Cell apoptosis and invasion were assessed by flow cytometry and transwell assay, respectively. Cellular glycolysis, including glucose consumption, lactate production, and ATP/ADP ratio, was detected by commercial kits. All protein levels were measured by western blot assay. The relationship between miR-338-3p and circ-TFF1 or FGFR1 was predicted by online bioinformatics tool and verified by dual-luciferase reporter assay. Xenograft tumor model was established to verify the function of circ-TFF1 in vivo. Circ-TFF1 was overexpressed in BC tissues and cells. Circ-TFF1 knockdown inhibited cell proliferation, invasion and glycolysis and induced apoptosis in BC cells. Circ-TFF1 acted as a sponge of miR-338-3p, and the effects of circ-TFF1 knockdown on BC cell proliferation, apoptosis, invasion, and glycolysis were abolished by miR-338-3p inhibition. FGFR1 was confirmed to be a target gene of miR-338-3p, and miR-338-3p played a tumor-suppressive role in BC by targeting FGFR1. Moreover, circ-TFF1 regulated FGFR1 expression by targeting miR-338-3p. Additionally, circ-TFF1 knockdown hampered tumorigenesis in vivo. Circ-TFF1 knockdown suppressed BC progression by regulating miR-338-3p/FGFR1 axis, providing a promising therapeutic target for BC.

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Data Availability

Please contact the correspondence author for the data request. The data that support the findings of this study are available from the corresponding author.

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Authors and Affiliations

  1. Department of Ultrasound, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, Hubei Province, China

    Long Wan & Zhihua Kong

  2. Department of Oncology, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, Hubei Province, China

    Qi Han & Bisheng Zhu

  3. Department of Ultrasound, Xianning Hospital of Traditional Chinese Medicine, No.17 Binhe West Street, Xian’an District, Xianning, 437000, Hubei Province, China

    Enrong Feng

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  1. Long Wan
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  2. Qi Han
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  3. Bisheng Zhu
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  4. Zhihua Kong
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  5. Enrong Feng
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Correspondence to Enrong Feng.

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Written informed consent was obtained from patients with approval by the Institutional Review Board in Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology.

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10528_2021_10102_MOESM1_ESM.tif

Supplementary file1 (TIF 66 kb) Knockdown of circ-TFF1 inhibited GLUT1 protein expression in BC cells. The protein expression of GLUT1 was detected by western blot assay in BT-549 and MDA-MB-231 cells transfected with si–N or si-circ-TFF1. ***P < 0.001.

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Wan, L., Han, Q., Zhu, B. et al. Circ-TFF1 Facilitates Breast Cancer Development via Regulation of miR-338-3p/FGFR1 Axis. Biochem Genet 60, 315–335 (2022). https://doi.org/10.1007/s10528-021-10102-6

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  • DOI: https://doi.org/10.1007/s10528-021-10102-6

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