EIF4A3-regulated Circ_0087429 Can Reverse EMT and Inhibit the Progression of Cervical Cancer Via MiR-5003-3p-dependent Upregulation of OGN Expression

Overview

Journal J Exp Clin Cancer Res

Publisher Biomed Central

Specialty Oncology

Date 2022 May 5

PMID 35513835

Authors

Meiqin Yang

Haoran Hu

Sufang Wu

Jianyi Ding

Bo Yin

Baoyou Huang

Fang Li

Xiaoqing Guo

Lingfei Han

Affiliations

Soon will be listed here.

Abstract

Background: Circular RNAs (circRNAs) are noncoding RNAs with stable structures with high expression and tissue-specific expression. Studies have shown that circRNA dysregulation is closely related to the progression of tumours. However, the function and regulatory mechanism of most circRNAs in cervical cancer are still unclear. METHODS: CircRNAs related to cervical cancer were screened through the Gene Expression Omnibus (GEO) database. qRT-PCR was used to verify the expression of circ_0087429 in cervical cancer tissues and cells. Then, in vivo and in vitro experiments were conducted to evaluate the role of circ_0087429 in the progression of cervical cancer. The role of the circ_0087429/miR-5003-3p/osteoglycin (OGN) axis in the epithelial to mesenchymal transition (EMT) was confirmed by rescue experiments, fluorescence in situ hybridization, luciferase reporter assays, immunofluorescence staining and western blotting. The inhibitory effect of Eukaryotic initiation factor 4A-III (EIF4A3) on the biogenesis of circ_0087429 was verified by RNA immunoprecipitation (RIP) assays and qRT-PCR.

Results: circ_0087429 is significantly downregulated in cervical cancer tissues and cells and negatively correlated with International Federation of Gynecology and Obstetrics (FIGO) staging and lymphatic metastasis in cervical cancer patients. circ_0087429 can significantly inhibit the proliferation, migration, invasion and angiogenesis of cervical cancer in vitro and tumour growth and metastasis in vivo. OGN is significantly downregulated in cervical cancer tissues and cells. circ_0087429 can upregulate the expression of OGN by competitively binding with miR-5003-3p, thereby reversing EMT and inhibiting the progression of cervical cancer. EIF4A3 can inhibit circ_0087429 expression by binding to its flanking regions.

Conclusions: As a tumour suppressor, circ_0087429 regulated by EIF4A3 can reverse EMT and inhibit the progression of cervical cancer through the miR-5003-3p/OGN axis. It is expected to become a potential target for the treatment of cervical cancer.

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References

Mazloomian A, Araki S, Ohori M, El-Naggar A, Yap D, Bashashati A . Pharmacological systems analysis defines EIF4A3 functions in cell-cycle and RNA stress granule formation. Commun Biol. 2019; 2:165. PMC: 6499833. DOI: 10.1038/s42003-019-0391-9. View

Simms K, Hanley S, Smith M, Keane A, Canfell K . Impact of HPV vaccine hesitancy on cervical cancer in Japan: a modelling study. Lancet Public Health. 2020; 5(4):e223-e234. DOI: 10.1016/S2468-2667(20)30010-4. View

Lomnytska M, Becker S, Hellman K, Hellstrom A, Souchelnytskyi S, Mints M . Diagnostic protein marker patterns in squamous cervical cancer. Proteomics Clin Appl. 2010; 4(1):17-31. DOI: 10.1002/prca.200900086. View

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

Bai F, Zhang L, Liu X, Wang C, Zheng C, Sun J . GATA3 functions downstream of BRCA1 to suppress EMT in breast cancer. Theranostics. 2021; 11(17):8218-8233. PMC: 8344017. DOI: 10.7150/thno.59280. View

Xu J, Zhang Y, Huang Y, Dong X, Xiang Z, Zou J . circEYA1 Functions as a Sponge of miR-582-3p to Suppress Cervical Adenocarcinoma Tumorigenesis via Upregulating CXCL14. Mol Ther Nucleic Acids. 2020; 22:1176-1190. PMC: 7701031. DOI: 10.1016/j.omtn.2020.10.026. View

Xu T, Zhang R, Dong M, Zhang Z, Li H, Zhan C . Osteoglycin (OGN) Inhibits Cell Proliferation and Invasiveness in Breast Cancer via PI3K/Akt/mTOR Signaling Pathway. Onco Targets Ther. 2019; 12:10639-10650. PMC: 6900314. DOI: 10.2147/OTT.S222967. View

Zhou M, Yang Z, Wang D, Chen P, Zhang Y . The circular RNA circZFR phosphorylates Rb promoting cervical cancer progression by regulating the SSBP1/CDK2/cyclin E1 complex. J Exp Clin Cancer Res. 2021; 40(1):48. PMC: 7846991. DOI: 10.1186/s13046-021-01849-2. View

Liu M, Wang Q, Shen J, Yang B, Ding X . Circbank: a comprehensive database for circRNA with standard nomenclature. RNA Biol. 2019; 16(7):899-905. PMC: 6546381. DOI: 10.1080/15476286.2019.1600395. View

10.

Hu X, Li Y, Li Q, Ma Y, Peng J, Cai S . Osteoglycin (OGN) reverses epithelial to mesenchymal transition and invasiveness in colorectal cancer via EGFR/Akt pathway. J Exp Clin Cancer Res. 2018; 37(1):41. PMC: 5833032. DOI: 10.1186/s13046-018-0718-2. View

11.

Tulchinsky E, Demidov O, Kriajevska M, Barlev N, Imyanitov E . EMT: A mechanism for escape from EGFR-targeted therapy in lung cancer. Biochim Biophys Acta Rev Cancer. 2018; 1871(1):29-39. DOI: 10.1016/j.bbcan.2018.10.003. View

12.

Luo Z, Rong Z, Zhang J, Zhu Z, Yu Z, Li T . Circular RNA circCCDC9 acts as a miR-6792-3p sponge to suppress the progression of gastric cancer through regulating CAV1 expression. Mol Cancer. 2020; 19(1):86. PMC: 7210689. DOI: 10.1186/s12943-020-01203-8. View

13.

Mukhopadhyay S, Vander Heiden M, McCormick F . The Metabolic Landscape of RAS-Driven Cancers from biology to therapy. Nat Cancer. 2021; 2(3):271-283. PMC: 8045781. DOI: 10.1038/s43018-021-00184-x. View

14.

Shi Q, Zhu Y, Ma J, Chang K, Ding D, Bai Y . Prostate Cancer-associated SPOP mutations enhance cancer cell survival and docetaxel resistance by upregulating Caprin1-dependent stress granule assembly. Mol Cancer. 2019; 18(1):170. PMC: 6878651. DOI: 10.1186/s12943-019-1096-x. View

15.

Kalliala I, Athanasiou A, Veroniki A, Salanti G, Efthimiou O, Raftis N . Incidence and mortality from cervical cancer and other malignancies after treatment of cervical intraepithelial neoplasia: a systematic review and meta-analysis of the literature. Ann Oncol. 2020; 31(2):213-227. PMC: 7479506. DOI: 10.1016/j.annonc.2019.11.004. View

16.

Li Q, Lei C, Lu C, Wang J, Gao M, Gao W . LINC01232 exerts oncogenic activities in pancreatic adenocarcinoma via regulation of TM9SF2. Cell Death Dis. 2019; 10(10):698. PMC: 6754375. DOI: 10.1038/s41419-019-1896-3. View

17.

Li H, Xu J, Fang X, Zhu J, Yang J, Pan R . Circular RNA circRNA_000203 aggravates cardiac hypertrophy via suppressing miR-26b-5p and miR-140-3p binding to Gata4. Cardiovasc Res. 2019; 116(7):1323-1334. PMC: 7243276. DOI: 10.1093/cvr/cvz215. View

18.

Pan G, Liu Y, Shang L, Zhou F, Yang S . EMT-associated microRNAs and their roles in cancer stemness and drug resistance. Cancer Commun (Lond). 2021; 41(3):199-217. PMC: 7968884. DOI: 10.1002/cac2.12138. View

19.

Pietraszek-Gremplewicz K, Karamanou K, Niang A, Dauchez M, Belloy N, Maquart F . Small leucine-rich proteoglycans and matrix metalloproteinase-14: Key partners?. Matrix Biol. 2017; 75-76:271-285. DOI: 10.1016/j.matbio.2017.12.006. View

20.

Dweep H, Sticht C, Pandey P, Gretz N . miRWalk--database: prediction of possible miRNA binding sites by "walking" the genes of three genomes. J Biomed Inform. 2011; 44(5):839-47. DOI: 10.1016/j.jbi.2011.05.002. View