Abstract
Circular RNAs are emerging players in human cancers, including esophageal squamous cell carcinoma (ESCC). Herein, we assessed the expression level of circ_0023990 and explored the molecular mechanisms of circ_0023990 in ESCC. circ_0023990, miR-6884-5p, and PAK1 expressions in ESCC tissues and cells were detected by quantitative real-time polymerase chain reaction and western blot. ESCC cells were transfected with different constructs to alter the expression of circ_0023990, miR-6884-5p, and PAK1. The effect of circ_0023990 on the proliferation, invasion, and glycolysis of ESCC cells was observed. The interaction between circ_0023990 and miR-6884-5p and between miR-6884-5p and PAK1 were explored. A mouse model of ESCC was established to study the in vivo effect of circ_0023990 knockdown on tumor formation.The expression levels of circ_0023990 was upregulated in ESCC tissues and cells. Inhibiting circ_0023990 suppressed the proliferation, invasion, and glycolysis of ESCC cells. circ_0023990 might target miR-6884-5p and consequently modulate the expression and activity of PAK1. Knockdown of circ_0023990 led to significantly reduced tumor volume and weight in mice with ESCC.These findings overall suggest an oncogenic role of circ_0023990 in ESCC. Future research is warranted to confirm the expression pattern and clinical significance of circ_0023990 in ESCC.
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The datasets generated during and/or analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request.
References
Allen JW, Richardson JD, Edwards MJ (1997) Squamous cell carcinoma of the esophagus: a review and update. Surg Oncol 6(4):193–200
Feng Q, Zhang H, Yao D, Chen WD, Wang YD (2019) Emerging role of non-coding RNAs in esophageal squamous cell carcinoma. Int J Mol Sci ;21(1)
Gan J, Zhang Y, Ke X et al (2015) Dysregulation of PAK1 is Associated with DNA damage and is of Prognostic Importance in primary esophageal small cell carcinoma. Int J Mol Sci 16(6):12035–12050
Huang FL, Yu SJ (2018) Esophageal cancer: risk factors, genetic association, and treatment. Asian J Surg 41(3):210–215
Kato Y, Maeda T, Suzuki A, Baba Y (2018) Cancer metabolism: new insights into classic characteristics. Jpn Dent Sci Rev 54(1):8–21
Khan S, Jha A, Panda AC, Dixit A (2021) Cancer-Associated circRNA-miRNA-mRNA Regulatory networks: a Meta-analysis. Front Mol Biosci 8:671309
Kristensen LS, Hansen TB, Venø MT, Kjems J (2018) Circular RNAs in cancer: opportunities and challenges in the field. Oncogene 37(5):555–565
Lv H, Hou H, Lei H et al (2020) MicroRNA-6884-5p regulates the Proliferation, Invasion, and EMT of gastric Cancer cells by directly targeting S100A16. Oncol Res 28(3):225–236
Napier KJ, Scheerer M, Misra S (2014) Esophageal cancer: a review of epidemiology, pathogenesis, staging workup and treatment modalities. World J Gastrointest Oncol 6(5):112–120
Panda AC (2018) Circular RNAs act as miRNA sponges. Adv Exp Med Biol 1087:67–79
Qiang G, Yu Q, Su K, Guo Y, Liu D, Liang C (2022) E2F1-activated LINC01224 drives esophageal squamous cell carcinoma cell malignant behaviors via targeting miR-6884-5p/DVL3 axis and activating Wnt/β-catenin signaling pathway. Pathol Res Pract 235:153873
Shan C, Zhang Y, Hao X, Gao J, Chen X, Wang K (2019) Biogenesis, functions and clinical significance of circRNAs in gastric cancer. Mol Cancer 18(1):136
Sheikh M, Roshandel G, McCormack V, Malekzadeh R (2023) Current status and future prospects for esophageal Cancer. Cancers (Basel) ;15(3)
Tustumi F, Kimura CM, Takeda FR et al (2016) PROGNOSTIC FACTORS AND SURVIVAL ANALYSIS IN ESOPHAGEAL CARCINOMA. Arq Bras Cir Dig 29(3):138–141
Vo JN, Cieslik M, Zhang Y et al (2019) The Landscape of circular RNA in Cancer. Cell 176(4):869–881e813
Wang X, Tao G, Huang D, Liang S, Zheng D, Circular (2020) RNA NOX4 promotes the development of colorectal cancer via the microRNA–485–5p/CKS1B axis. Oncol Rep 44(5):2009–2020
Zhang HD, Jiang LH, Sun DW, Hou JC, Ji ZL (2018) CircRNA: a novel type of biomarker for cancer. Breast Cancer 25(1):1–7
Zhang Q, Wu L, Liu SZ, Chen QJ, Zeng LP, Chen XZ (2021) Hsa_circ_0023990 promotes Tumor Growth and Glycolysis in Dedifferentiated TC via Targeting miR-485-5p/FOXM1 Axis. Endocrinology ;162(12)
Zhong H, Xu Y, Wang J, Cao Q, Hu L, Sun D (2021) Overexpression of microRNA-19a-3p promotes lymph node metastasis of esophageal squamous cell carcinoma via the RAC1/CDC42-PAK1 pathway. Transl Cancer Res 10(6):2694–2706
Zhu L, Yang F, Li X, Li Q, Zhong C (2021) Glycolysis changes the Microenvironment and Therapeutic Response under the driver of Gene Mutation in Esophageal Adenocarcinoma. Front Genet 12:743133
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Ningbo Natural Science Foundation(2017A610155). Zhejiang Medical and Health Science and Technology Project(2020KY867). NINGBO Medical & Health Leading Academic Discipline Project(Project Number:2022-F02).
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Conception and design: Jinxian He, Hui Tian, Gaofeng Liang. Data analysis and interpretation: Hui Tian, Gaofeng Liang, Qi Qin. Manuscript writing: Jinxian He, Hui Tian, Chaoqun Yu. Final approval of manuscript: All authors.
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Written informed consent was obtained from each patient included in the study and the study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the Ethics Committee of Ningbo Medical Center Lihuili Hospital. Each animal experimental procedure gained approval from Animal Ethics Committee of Ningbo Medical Center Lihuili Hospital. The experimental protocol was performed in accordance with the relevant guidelines and regulations of the Basel Declaration. The study is reported in accordance with ARRIVE guidelines (https://arriveguidelines.org).
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Tian, H., Liang, G., Qin, Q. et al. Circ_0023990 Promotes the Proliferation, Invasion, and Glycolysis of Esophageal Squamous Cell Carcinoma Cells Via Targeting miR-6884-5p/PAK1 Axis. Biochem Genet (2024). https://doi.org/10.1007/s10528-024-10674-z
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DOI: https://doi.org/10.1007/s10528-024-10674-z