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CircRNA circ-OGDH (hsa_circ_0003340) Acts as a ceRNA to Regulate Glutamine Metabolism and Esophageal Squamous Cell Carcinoma Progression by the miR-615-5p/PDX1 Axis

Authors Liang Z, Zhao B, Hou J, Zheng J, Xin G

Received 2 November 2020

Accepted for publication 1 March 2021

Published 7 April 2021 Volume 2021:13 Pages 3041—3053

DOI https://doi.org/10.2147/CMAR.S290088

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Sanjeev Srivastava


Zongying Liang, Baoshan Zhao, Jishen Hou, Jingxiong Zheng, Guohua Xin

Department of Thoracic Surgery, The Affiliated Hospital of Chengde Medical University, Chengde, 067000, People’s Republic of China

Correspondence: Guohua Xin
Department of Thoracic Surgery, The Affiliated Hospital of Chengde Medical University, No. 36, Nanyingzi Street, Shuangqiao District, Chengde, 067000, People’s Republic of China
Email [email protected]

Background: Circular RNA hsa_circ_0003340 (circ-OGDH) has been uncovered to be involved in esophageal squamous cell carcinoma (ESCC) progression. However, the mechanism by which circ-OGDH regulates ESCC progression is unclear.
Methods: Expression levels of circ-OGDH, microRNA (miR)-615-5p, and PDX1 (pancreatic and duodenal homeobox 1) mRNA were evaluated with quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation, apoptosis, migration, invasion, and cell cycle progression of ESCC cells were analyzed by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide), colony formation, flow cytometry, and transwell assays. Measurement of glutamine consumption, α-KG (α-ketoglutarate) production, and ATP (Adenosine Triphosphate) content using corresponding kits. Protein levels were analyzed by Western blotting. The targeting relationship between circ-OGDH or PDX1 and miR-615-5p was verified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. The function of circ-OGDH in ESCC was confirmed by animal experiments.
Results: Circ-OGDH was upregulated in ESCC. Circ-OGDH inhibition reduced ESCC growth in vivo and accelerated cell apoptosis, cell cycle arrest, repressed cell proliferation, migration, invasion, and reduced cell glutamine metabolism in ESCC cells in vitro. MiR-615-5p was downregulated in ESCC, while PDX1 had an opposite result. Circ-OGDH sponged miR-615-5p to regulate PDX1 expression. MiR-615-5p inhibitor neutralized the repressive effect of circ-OGDH knockdown on malignancy and glutamine metabolism of ESCC cells. PDX1 overexpression counteracted the inhibitory impact of miR-615-5p mimic on malignancy and glutamine metabolism of ESCC cells.
Conclusion: Circ-OGDH sponged miR-615-5p to elevate PDX1 expression, thus elevating glutamine metabolism and promoting tumor growth in ESCC. The study offered evidence to support circ-OGDH as a promising target for ESCC therapy.

Keywords: ESCC, circ-OGDH, miR-615-5p, PDX1, glutamine

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