RETRACTED ARTICLE: Circ_0008035 contributes to cell proliferation and inhibits apoptosis and ferroptosis in gastric cancer via miR-599/EIF4A1 axis

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.

Crosstalk between noncoding RNAs and ferroptosis: new dawn for overcoming cancer progression

“…Furthermore, circ0008035 inhibited ferroptosis in gastric cancer via miR-599 /EIF4A1 axis. Knockdown of circ0008035 enhanced anticancer effect of erastin and RSL3 via increased iron accumulation and lipid peroxidation 156 . According to ferroptosis associated factors, in gastric cancer, circPVT1 promoted multidrug resistance by enhancing P-gp and GSTP.…”

Regulation of ferroptosis by ncRNA: A new direction

“…Li et al found that Circ_0008035 promoted GC cell growth and repressed apoptosis and ferroptosis by upregulating EIF4A1 through sponging miR-599. 64 In addition, Zhang et al prove that exosome-miR-522 serves as a potential inhibitor of ALOX15. Further study demonstrates that Cancer-associated fibroblasts secrete exosome miR-522 to inhibit ferroptosis in cancer cells by targeting ALOX15 and blocking lipid-ROS accumulation.…”

Bupivacaine suppresses the progression of gastric cancer through regulating circ_0000376/miR-145-5p axis

“…Among these ncRNAs, circular RNAs (circRNAs) are ideal biomarkers for human diseases due to their covalently closed loop structure [ 13 ]. Li et al claimed that circ_0008035 accelerated the progression of gastric cancer through regulating microRNA-599 (miR-599)/EIF4A1 axis [ 14 ]. CircPIP5K1A contributed to the development of gastric cancer through targeting miR-376c-3p/ZNF146 signaling [ 15 ].…”