Functional Elucidation of the EIF4A3-circR-4225-miR-507-TNFSF11 Regulatory Axis in LUAD and Its Role in Tumor Progression

Overview

Journal Sci Rep

Specialty Science

Date 2024 Aug 28

PMID 39198460

Authors

Guoqiang Wang

Zijuan Zhang

Jiaxing Wang

Lu Kang

Guanmin Zheng

Baoguang Liu

Jiezhi Yang

Yangang Sun

Huahui Zeng

Zhenqiang Zhang

Affiliations

Soon will be listed here.

Abstract

Lung adenocarcinoma (LUAD) is the most common subtypes of NSCLC. However, the therapeutic effects for LUAD are unsatisfactory at current stage, so it is important to find new molecular targets and therapeutic strategies. circRNAs can regulate the expression of target genes by binding to microRNAs (miRNAs) to form competitive endogenous RNAs (ceRNAs). Therefore, we investigated the functions of circR-4225 in the tumor progression of LUAD and its molecular mechanism in this paper. circR-4225 is up-regulated in LUAD tissues. EIF4A3, a member of the eukaryotic translation initiation factor 4A (EIF4A) family, promotes the expression of circR-4225. circR-4225 acts as a molecular sponge to down-regulate miR-507, which promotes the up-regulation of the expression of its target gene-tumor necrosis factor superfamily member 11 (TNFSF11). Knockdown of circR-4225 in the LUAD cell lines can inhibit cell proliferation and viability, and promote apoptosis of the LUAD cell lines, which can be reverted by inhibiting miR-507 or overexpressing TNFSF11. To sum it up, this study demonstrated that circR-4225 was significantly up-regulated in LUAD tissues, and circR-4225 promoted LUAD progression by sponging miR-507 and up-regulating TNFSF11. This study can provide new molecular targets for early diagnosis and treatment of LUAD.

References

Zhang P, Dai M . CircRNA: a rising star in plant biology. J Genet Genomics. 2022; 49(12):1081-1092. DOI: 10.1016/j.jgg.2022.05.004. View

Zhang S, Leng T, Zhang Q, Zhao Q, Nie X, Yang L . Sanguinarine inhibits epithelial ovarian cancer development via regulating long non-coding RNA CASC2-EIF4A3 axis and/or inhibiting NF-κB signaling or PI3K/AKT/mTOR pathway. Biomed Pharmacother. 2018; 102:302-308. DOI: 10.1016/j.biopha.2018.03.071. View

Rubio C, Weisburd B, Holderfield M, Arias C, Fang E, DeRisi J . Transcriptome-wide characterization of the eIF4A signature highlights plasticity in translation regulation. Genome Biol. 2014; 15(10):476. PMC: 4203936. DOI: 10.1186/s13059-014-0476-1. View

Zheng Y, Ji P, Chen S, Hou L, Zhao F . Reconstruction of full-length circular RNAs enables isoform-level quantification. Genome Med. 2019; 11(1):2. PMC: 6339429. DOI: 10.1186/s13073-019-0614-1. View

Giorgi C, Moore M . The nuclear nurture and cytoplasmic nature of localized mRNPs. Semin Cell Dev Biol. 2007; 18(2):186-93. DOI: 10.1016/j.semcdb.2007.01.002. View

Zhu C, Su Y, Liu L, Wang S, Liu Y, Wu J . Circular RNA hsa_circ_0004277 Stimulates Malignant Phenotype of Hepatocellular Carcinoma and Epithelial-Mesenchymal Transition of Peripheral Cells. Front Cell Dev Biol. 2021; 8:585565. PMC: 7835424. DOI: 10.3389/fcell.2020.585565. View

Reed R . Coupling transcription, splicing and mRNA export. Curr Opin Cell Biol. 2003; 15(3):326-31. DOI: 10.1016/s0955-0674(03)00048-6. View

Tang W, Wang D, Shao L, Liu X, Zheng J, Xue Y . LINC00680 and TTN-AS1 Stabilized by EIF4A3 Promoted Malignant Biological Behaviors of Glioblastoma Cells. Mol Ther Nucleic Acids. 2020; 19:905-921. PMC: 7063483. DOI: 10.1016/j.omtn.2019.10.043. View

Zhang Y, Qi W, Wu Y . EIF4A3-induced circular RNA SCAP facilitates tumorigenesis and progression of non-small-cell lung cancer via miR-7/SMAD2 signaling. Environ Sci Pollut Res Int. 2023; 30(24):65237-65249. PMC: 10182944. DOI: 10.1007/s11356-023-26307-8. View

10.

Ren S, Lin P, Wang J, Yu H, Lv T, Sun L . Circular RNAs: Promising Molecular Biomarkers of Human Aging-Related Diseases via Functioning as an miRNA Sponge. Mol Ther Methods Clin Dev. 2020; 18:215-229. PMC: 7326721. DOI: 10.1016/j.omtm.2020.05.027. View

11.

Chen L . The biogenesis and emerging roles of circular RNAs. Nat Rev Mol Cell Biol. 2016; 17(4):205-11. DOI: 10.1038/nrm.2015.32. View

12.

Fan C, Qu H, Xiong F, Tang Y, Tang T, Zhang L . CircARHGAP12 promotes nasopharyngeal carcinoma migration and invasion via ezrin-mediated cytoskeletal remodeling. Cancer Lett. 2020; 496:41-56. DOI: 10.1016/j.canlet.2020.09.006. View

13.

Siegel R, Miller K, Fuchs H, Jemal A . Cancer Statistics, 2021. CA Cancer J Clin. 2021; 71(1):7-33. DOI: 10.3322/caac.21654. View

14.

Chandler B, Hayashi M, HAYASHI M, Spiegelman S . CIRCULARITY OF THE REPLICATING FORM OF A SINGLE-STRANDED DNA VIRUS. Science. 1964; 143(3601):47-9. DOI: 10.1126/science.143.3601.47. View

15.

Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi P . A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language?. Cell. 2011; 146(3):353-8. PMC: 3235919. DOI: 10.1016/j.cell.2011.07.014. View

16.

Liu Z, Liu F, Wang F, Yang X, Guo W . CircZNF609 promotes cell proliferation, migration, invasion, and glycolysis in nasopharyngeal carcinoma through regulating HRAS via miR-338-3p. Mol Cell Biochem. 2020; 476(1):175-186. DOI: 10.1007/s11010-020-03894-5. View

17.

Zheng X, Huang M, Xing L, Yang R, Wang X, Jiang R . The circRNA circSEPT9 mediated by E2F1 and EIF4A3 facilitates the carcinogenesis and development of triple-negative breast cancer. Mol Cancer. 2020; 19(1):73. PMC: 7137343. DOI: 10.1186/s12943-020-01183-9. View

18.

Zhang Z, Yang T, Xiao J . Circular RNAs: Promising Biomarkers for Human Diseases. EBioMedicine. 2018; 34:267-274. PMC: 6116471. DOI: 10.1016/j.ebiom.2018.07.036. View

19.

Yao Z, Xu R, Yuan L, Xu M, Zhuang H, Li Y . Circ_0001955 facilitates hepatocellular carcinoma (HCC) tumorigenesis by sponging miR-516a-5p to release TRAF6 and MAPK11. Cell Death Dis. 2019; 10(12):945. PMC: 6904727. DOI: 10.1038/s41419-019-2176-y. View

20.

Wan L, Zhang L, Fan K, Cheng Z, Sun Q, Wang J . Circular RNA-ITCH Suppresses Lung Cancer Proliferation via Inhibiting the Wnt/β-Catenin Pathway. Biomed Res Int. 2016; 2016:1579490. PMC: 5013215. DOI: 10.1155/2016/1579490. View