Circ_0008035 contributes to cell proliferation and inhibits apoptosis and ferroptosis in gastric cancer via miR-599/EIF4A1 axis
Authors: Qingchun Li
Yun Liang
Chang Li
Yuan Tian
Journal: Cancer Cell International (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Apoptosis; Circ_0008035; EIF4A1; Ferroptosis; Gastric cancer
Affiliations: 1Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, No.126, Xiantai Street, Changchun, 130031 Jilin China., 2Center of Physical Examination, China-Japan Union Hospital of Jilin University, Changchun, 130031 Jilin China.

Abstract:  Background: Currently, multiple circular RNAs (circRNAs) have been verified to act as essential regulators in the progression of gastric cancer (GC). We aimed to investigate the role of circ_0008035 in GC progression. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to measure the expression of circ_0008035 and miR-599. 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay was employed to evaluate cell proliferation and ferroptosis. Western blot assay was performed to measure the levels of cyclin D1, proliferating cell nuclear antigen (PCNA) and eukaryotic initiation factor 4A1 (EIF4A1). Flow cytometry analysis was conducted to assess cell apoptosis. The iron accumulation, lipid peroxidation and mitochondrial membrane potential were examined by relevant kits. Dual-luciferase reporter assay was conducted to determine the targeting relationship between miR-599 and circ_0008035 or EIF4A1. A murine xenograft model was established to investigate the function of circ_0008035 in vivo. Results: Circ_0008035 was up-regulated in GC tissues and cells. Silencing of circ_0008035 repressed cell proliferation and induced cell apoptosis and ferroptosis in GC cells. Circ_0008035 acted as a sponge of miR-599. The effects of circ_0008035 knockdown on GC cell proliferation, apoptosis and ferroptosis were abolished by miR-599 inhibition. EIF4A1 was confirmed to be a target gene of miR-599. Circ_0008035 knockdown inhibited EIF4A1 expression by targeting miR-599. Moreover, the suppressive role of circ_0008035 deficiency in GC progression could be restored by EIF4A1. Additionally, circ-0008035 knockdown hampered tumorigenesis in vivo. Conclusion: Circ_0008035 promoted GC cell growth and repressed apoptosis and ferroptosis by up-regulating EIF4A1 through sponging miR-599. 

Retracted: Yes

PubPeer comments:
 ![file] Figure 2e and Figure 2f look a bit similar , 
 Retracted, [9 August 2021] . -------------------------- The Editors-in-Chief have retracted this article. Concerns have been raised regarding a number of figures, specifically: - Figure 2e: the HGC-27 cyclin D1 panel appears to be identical to the AGS PCNA panel of Fig. 2f. - Figure 2e: the HGC-27 PCNA panel appears to be identical to the AGS cyclin D1 panel of Fig. 2f. - Figure 2e: the HGC-27 GAPDH panel appears to be identical to the AGS GAPDH panel of Fig. 2f. In addition, the authors have not provided documents confirming that ethics approval was obtained for this study. The Editors-in-Chief therefore no longer have confidence in the reliability of the data reported in the article. None of the authors have responded to any correspondence from the publisher about this retraction. ,