Icariin Regulates the Hsa_circ_0003159/eIF4A3/bcl-2 Axis to Promote Gastric Cancer Cell Apoptosis

Overview

Journal Evid Based Complement Alternat Med

Specialty Rehabilitation Medicine

Date 2022 Jul 25

PMID 35873631

Authors

Yanfen Yin

Wenwen Xu

Yanan Song

Zhou Zhou

Xin Sun

Fengli Zhang

Affiliations

Soon will be listed here.

Abstract

Objective: To clarify the mechanism of icariin (ICA) promoting gastric cancer (GC) cell apoptosis by regulating circ_0003159/eIF4A3/bcl-2 axis.

Methods: The mRNA or protein levels were detected by qRT-PCR or the western blot. The interaction between eIF4A3 protein and circ_0003159 or eIF4A3 protein and bcl-2 mRNA were validated by RNA pull down assays and the RNA immunoprecipitation (RIP) assay. The cell viability was measured by the cell counting kit (CCK)-8 kit. The cell apoptosis was measured by flow cytometry.

Results: Compared with the group Vector, the ratio of cytoplasmic eIF4A3/nuclear eIF4A3 in the cell with circ_0003159 overexpression was significantly higher. RIP and RNA pull down results proved the interaction between eIF4A3 and circ_0003159. The RIP assay further validated the interaction between eIF4A3 and bcl-2. By gain or loss of the functional experiment, hsa_circ_0003159 was proved to recruit eIF4A3 to inhibit bcl-2 expression. Hsa_circ_0003159 regulates eIF4A3/bcl-2 to reduce GC cell viability and increase apoptosis Furthermore, ICA regulates hsa_circ_0003159/eIF4A3/bcl-2 axis to inhibit GC cell activity and induce GC cell apoptosis .

Conclusion: These data showed that ICA could effectively reduce the GC cell activity and induce GC cell apoptosis via hsa_circ_0003159/eIF4A3/bcl-2 axis, which provides new theoretical evidence for the treatment of GC by ICA.

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References

Abbey E, Yang F, Qi L, Wu J, Tong L, Zhen Z . Situs inversus totalis patients with gastric cancer: Robotic surgery the standard of treatment?-A case report. Int J Surg Case Rep. 2021; 81:105818. PMC: 8050025. DOI: 10.1016/j.ijscr.2021.105818. View

Michelle L, Cloutier A, Toutant J, Shkreta L, Thibault P, Durand M . Proteins associated with the exon junction complex also control the alternative splicing of apoptotic regulators. Mol Cell Biol. 2011; 32(5):954-67. PMC: 3295189. DOI: 10.1128/MCB.06130-11. View

Song L, Chen X, Mi L, Liu C, Zhu S, Yang T . Icariin-induced inhibition of SIRT6/NF-κB triggers redox mediated apoptosis and enhances anti-tumor immunity in triple-negative breast cancer. Cancer Sci. 2020; 111(11):4242-4256. PMC: 7648025. DOI: 10.1111/cas.14648. View

Zu Y, Mu Y, Li Q, Zhang S, Yan H . Icariin alleviates osteoarthritis by inhibiting NLRP3-mediated pyroptosis. J Orthop Surg Res. 2019; 14(1):307. PMC: 6737611. DOI: 10.1186/s13018-019-1307-6. View

Tian M, Chen R, Li T, Xiao B . Reduced expression of circRNA hsa_circ_0003159 in gastric cancer and its clinical significance. J Clin Lab Anal. 2017; 32(3). PMC: 6817154. DOI: 10.1002/jcla.22281. View

He C, Wang Z, Shi J . Pharmacological effects of icariin. Adv Pharmacol. 2020; 87:179-203. DOI: 10.1016/bs.apha.2019.10.004. View

Wang Y, Dong H, Zhu M, Ou Y, Zhang J, Luo H . Icariin exterts negative effects on human gastric cancer cell invasion and migration by vasodilator-stimulated phosphoprotein via Rac1 pathway. Eur J Pharmacol. 2010; 635(1-3):40-8. DOI: 10.1016/j.ejphar.2010.03.017. View

Zhang F, Yin Y, Xu W, Song Y, Zhou Z, Sun X . Icariin inhibits gastric cancer cell growth by regulating the hsa_circ_0003159/miR-223-3p/NLRP3 signaling axis. Hum Exp Toxicol. 2022; 41:9603271221097363. DOI: 10.1177/09603271221097363. View

Hu L, Li L, Zhang H, Li Q, Jiang S, Qiu J . Inhibition of airway remodeling and inflammatory response by Icariin in asthma. BMC Complement Altern Med. 2019; 19(1):316. PMC: 6862818. DOI: 10.1186/s12906-019-2743-x. View

10.

Yu F, Zhang Y, Wang Z, Gong W, Zhang C . Hsa_circ_0030042 regulates abnormal autophagy and protects atherosclerotic plaque stability by targeting eIF4A3. Theranostics. 2021; 11(11):5404-5417. PMC: 8039966. DOI: 10.7150/thno.48389. View

11.

He J, Li Y, Han Z, Zhou J, Chen W, Lv Y . The CircRNA-ACAP2/Hsa-miR-21-5p/ Tiam1 Regulatory Feedback Circuit Affects the Proliferation, Migration, and Invasion of Colon Cancer SW480 Cells. Cell Physiol Biochem. 2018; 49(4):1539-1550. DOI: 10.1159/000493457. View

12.

Qian Z, Wang Y, Li Y, Li Y, Ling-Zhu , Yang D . Icariin prevents hypertension-induced cardiomyocyte apoptosis through the mitochondrial apoptotic pathway. Biomed Pharmacother. 2017; 88:823-831. DOI: 10.1016/j.biopha.2017.01.147. View

13.

Wang J, Lv W, Lin Z, Wang X, Bu J, Su Y . Hsa_circ_0003159 inhibits gastric cancer progression by regulating miR-223-3p/NDRG1 axis. Cancer Cell Int. 2020; 20:57. PMC: 7031989. DOI: 10.1186/s12935-020-1119-0. View

14.

Lin Y, Zhang J, Cai J, Liang R, Chen G, Qin G . Systematic Analysis of Gene Expression Alteration and Co-Expression Network of Eukaryotic Initiation Factor 4A-3 in Cancer. J Cancer. 2018; 9(24):4568-4577. PMC: 6299400. DOI: 10.7150/jca.27655. View

15.

Jeck W, Sharpless N . Detecting and characterizing circular RNAs. Nat Biotechnol. 2014; 32(5):453-61. PMC: 4121655. DOI: 10.1038/nbt.2890. View

16.

Li R, Jiang J, Shi H, Qian H, Zhang X, Xu W . CircRNA: a rising star in gastric cancer. Cell Mol Life Sci. 2019; 77(9):1661-1680. PMC: 11104848. DOI: 10.1007/s00018-019-03345-5. View

17.

Sui X, Wang Y, Liu H . hsa_circ_0101119 facilitates the progression of cervical cancer via an interaction with EIF4A3 to inhibit TCEAL6 expression. Mol Med Rep. 2021; 24(3). PMC: 8299197. DOI: 10.3892/mmr.2021.12293. View

18.

Zhang Y, Wei Y, Zhu Z, Gong W, Liu X, Hou Q . Icariin enhances radiosensitivity of colorectal cancer cells by suppressing NF-κB activity. Cell Biochem Biophys. 2014; 69(2):303-10. DOI: 10.1007/s12013-013-9799-x. View

19.

Song Z, Wu Y, Yang J, Yang D, Fang X . Progress in the treatment of advanced gastric cancer. Tumour Biol. 2017; 39(7):1010428317714626. DOI: 10.1177/1010428317714626. View

20.

Chaichian S, Shafabakhsh R, Mirhashemi S, Moazzami B, Asemi Z . Circular RNAs: A novel biomarker for cervical cancer. J Cell Physiol. 2019; 235(2):718-724. DOI: 10.1002/jcp.29009. View