Skip to content
2000
Volume 20, Issue 4
  • ISSN: 1574-8928
  • E-ISSN: 2212-3970

Abstract

Background

Eukaryotic Initiation Factor 3C (EIF3C) represents a pivotal translational initiation factor in eukaryotes and has been shown to facilitate the progression of various neoplasms. However, its mechanistic role in ovarian cancer remains elusive.

Methods

In this research, the expression of EIF3C in ovarian cancer tissues was investigated using immunohistochemistry. In addition, the assessments were made on changes in cellular proliferation, invasion, and apoptotic abilities by reducing the expression of EIF3C in ovarian cancer cells. By utilizing microarray analysis, a comparison was performed between the downregulated EIF3C group and the control group of ovarian cancer cells, revealing the genes that were expressed differently. Furthermore, the signalling pathways associated with cellular proliferation were validated. The functional role of EIF3C was investigated using a xenograft tumour model.

Results

The immunohistochemical analysis showed that elevated levels of EIF3C are linked to a negative prognosis in patients with ovarian cancer. Suppression of EIF3C greatly hindered the growth and spread of SK-OV-3 and HO-8910 cells while enhancing cellular programmed cell death. Following KEGG and GSEA enrichment analyses of differentially expressed genes, the p53 signalling pathway was found to be associated with EIF3C. Suppression of EIF3C resulted in the upregulation of the p53 signalling pathway, leading to the inhibition of cell proliferation and invasion and the promotion of apoptosis. experiments demonstrated that EIF3C knockdown suppressed the growth of subcutaneous tumours in nude mice.

Conclusion

There is a correlation between overexpression of EIF3C in tumour tissues of ovarian cancer patients and this is associated with a poorer prognosis. By influencing the p53 signaling pathway, EIF3C facilitates the growth and infiltration of cells in ovarian cancer.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/pra/10.2174/0115748928292248240401051408
2024-04-15
2025-12-25

  • From This Site

    /content/journals/pra/10.2174/0115748928292248240401051408
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. SiegelR.L. MillerK.D. FuchsH.E. JemalA. Cancer statistics, 2022.CA Cancer J. Clin.202272173310.3322/caac.2170835020204
     [Google Scholar]
  2. LheureuxS. BraunsteinM. OzaA.M. Epithelial ovarian cancer: Evolution of management in the era of precision medicine.CA Cancer J. Clin.201969428030410.3322/caac.2155931099893
     [Google Scholar]
  3. YousefiM. DehghaniS. NosratiR. GhaneiM. SalmaninejadA. RajaieS. HasanzadehM. PasdarA. Current insights into the metastasis of epithelial ovarian cancer - Hopes and hurdles.Cell Oncol.202043451553810.1007/s13402‑020‑00513‑932418122
     [Google Scholar]
  4. WebbP.M. JordanS.J. Epidemiology of epithelial ovarian cancer.Best Pract. Res. Clin. Obstet. Gynaecol.20174131410.1016/j.bpobgyn.2016.08.00627743768
     [Google Scholar]
  5. TongY.G. TangY.J. LuoG.D. A method, system, and reagent kit for the early screening of ovarian cancer and the prognostication of recurrence.CN Patent 2022110159542023
  6. ZhaoY. YeH. WangP. Biomarker for ovarian cancer diagnosis and detection kit.CN Patent 2022107867852022
  7. SalaheldinY.A. MahmoudS.S.M. NgowiE.E. GbordzorV.A. LiT. WuD.D. JiX.Y. Role of RONS and eIFs in cancer progression.Oxid. Med. Cell. Longev.2021202111410.1155/2021/552205434285764
     [Google Scholar]
  8. WagnerS. HerrmannováA. HronováV. GunišováS. SenN.D. HannanR.D. HinnebuschA.G. ShirokikhN.E. PreissT. ValášekL.S. Selective translation complex profiling reveals staged initiation and co-translational assembly of initiation factor complexes.Mol. Cell2020794546560.e710.1016/j.molcel.2020.06.00432589964
     [Google Scholar]
  9. AliM.U. RahmanU.M.S. JiaZ. JiangC. Eukaryotic translation initiation factors and cancer.Tumour Biol.201739610.1177/101042831770980528653885
     [Google Scholar]
  10. HersheyJ.W.B. Regulation of protein synthesis and the role of eIF3 in cancer.Braz. J. Med. Biol. Res.2010431092093010.1590/S0100‑879X201000750009820922269
     [Google Scholar]
  11. SchwarzlG.N. SchweigerC. KollerC. KrassnigS. Gogg-KamererM. GantenbeinN. ToeglhoferA.M. WodlejC. BerglerH. PertschyB. UranitschS. HolterM. HeliebiE.A. FuchsJ. PunschartA. StieglerP. KeilM. HoffmannJ. HendersonD. LehrachH. ReinhardC. RegenbrechtC. SchichoR. FickertP. LaxS. HaybaeckJ. Separation of low and high grade colon and rectum carcinoma by eukaryotic translation initiation factors 1, 5 and 6.Oncotarget201786010122410124310.18632/oncotarget.2064229254159
     [Google Scholar]
  12. EmmanuelR. WeinsteinS. Landesman-MiloD. PeerD. eIF3c: A potential therapeutic target for cancer.Cancer Lett.2013336115816610.1016/j.canlet.2013.04.02623623922
     [Google Scholar]
  13. CateJH Human eIF3: From 'blobology' to biological insight.Philos Trans R Soc Lond B Biol Sci171637217162016017610.1098/rstb.2016.0176
     [Google Scholar]
  14. LiT. LiS. ChenD. ChenB. YuT. ZhaoF. WangQ. YaoM. HuangS. ChenZ. HeX. Transcriptomic analyses of RNA-binding proteins reveal eIF 3c promotes cell proliferation in hepatocellular carcinoma.Cancer Sci.2017108587788510.1111/cas.1320928231410
     [Google Scholar]
  15. HaoJ. WangZ. WangY. LiangZ. ZhangX. ZhaoZ. JiaoB. Eukaryotic initiation factor 3C silencing inhibits cell proliferation and promotes apoptosis in human glioma.Oncol. Rep.20153362954296210.3892/or.2015.388125823503
     [Google Scholar]
  16. ZhaoQ. LuoX. LiH. BaiY. ChenQ. YangM. PeiB. XuC. HanS. Targeting EIF3C to suppress the development and progression of nasopharyngeal carcinoma.Front. Bioeng. Biotechnol.20221099462810.3389/fbioe.2022.99462836147539
     [Google Scholar]
  17. ScolesD.R. YongW.H. QinY. WawrowskyK. PulstS.M. Schwannomin inhibits tumorigenesis through direct interaction with the eukaryotic initiation factor subunit c (eIF3c).Hum. Mol. Genet.20061571059107010.1093/hmg/ddl02116497727
     [Google Scholar]
  18. JiaoH. ZengL. YangS. ZhangJ. LouW. Knockdown EIF3C suppresses cell proliferation and increases apoptosis in pancreatic cancer cell.Dose Response202018310.1177/155932582095006132973416
     [Google Scholar]
  19. SongN. WangY. GuX. ChenZ. ShiL. Effect of siRNA-mediated knockdown of eIF3c gene on survival of colon cancer cells.J. Zhejiang Univ. Sci. B201314645145910.1631/jzus.B120023023733421
     [Google Scholar]
  20. FanM. WangK. WeiX. YaoH. ChenZ. HeX. Upregulated expression of eIF3C is associated with malignant behavior in renal cell carcinoma.Int. J. Oncol.20195561385139510.3892/ijo.2019.490331638200
     [Google Scholar]
  21. ZhaoW. LiX. WangJ. WangC. JiaY. YuanS. HuangY. ShiY. TongZ. Decreasing eukaryotic initiation factor 3C (EIF3C) suppresses proliferation and stimulates apoptosis in breast cancer cell lines through mammalian target of rapamycin (mTOR) pathway.Med. Sci. Monit.2017234182419110.12659/MSM.90638928854163
     [Google Scholar]
  22. WenF. WuZ.Y. NieL. ZhangQ.Z. QinY.K. ZhouZ. WuJ.J. ZhaoX. TanJ. SawmillerD. ZiD. Eukaryotic initiation factor 3, subunit C silencing inhibits cell proliferation and promotes apoptosis in human ovarian cancer cells.Biosci. Rep.2019398BSR2019112410.1042/BSR2019112431316002
     [Google Scholar]
  23. ChenJ. The cell-cycle arrest and apoptotic functions of p53 in tumor initiation and progression.Cold Spring Harb. Perspect. Med.201663a02610410.1101/cshperspect.a02610426931810
     [Google Scholar]
  24. WangH. GuoM. WeiH. ChenY. Targeting p53 pathways: Mechanisms, structures, and advances in therapy.Signal Transduct. Target. Ther.2023819210.1038/s41392‑023‑01347‑136859359
     [Google Scholar]
  25. ZhuJ. SinghM. SelivanovaG. PeugetS. Pifithrin-α alters p53 post-translational modifications pattern and differentially inhibits p53 target genes.Sci. Rep.2020101104910.1038/s41598‑020‑58051‑131974452
     [Google Scholar]
  26. GuoJ. TangQ. WangQ. SunW. PuZ. WangJ. BaoY. Pifithrin-α enhancing anticancer effect of topotecan on p53-expressing cancer cells.Eur. J. Pharm. Sci.2019128617210.1016/j.ejps.2018.11.02430472223
     [Google Scholar]
  27. SonenbergN. HinnebuschA.G. Regulation of translation initiation in eukaryotes: Mechanisms and biological targets.Cell2009136473174510.1016/j.cell.2009.01.04219239892
     [Google Scholar]
  28. KoubaT. RutkaiE. KaráskováM. ValášekL.S. The eIF3c/NIP1 PCI domain interacts with RNA and RACK1/ASC1 and promotes assembly of translation preinitiation complexes.Nucleic Acids Res.20124062683269910.1093/nar/gkr108322123745
     [Google Scholar]
  29. HuJ. LuoH. XuY. LuoG. XuS. ZhuJ. SongD. SunZ. KuangY. The prognostic significance of EIF3C gene during the tumorigenesis of prostate cancer.Cancer Invest.2019374-519920810.1080/07357907.2019.161832231181967
     [Google Scholar]
  30. LeeH.Y. ChenC.K. HoC.M. LeeS.S. ChangC.Y. ChenK.J. JouY.S. EIF3C-enhanced exosome secretion promotes angiogenesis and tumorigenesis of human hepatocellular carcinoma.Oncotarget2018917131931320510.18632/oncotarget.2414929568350
     [Google Scholar]
  31. XuY.P. DongZ.N. ZhouY.Q. ZhaoY.J. ZhaoY. WangF. HuangX.Y. GuoC.Y. Role of eIF3C overexpression in predicting prognosis of intrahepatic cholangiocarcinoma.Dig. Dis. Sci.202267255956810.1007/s10620‑021‑06878‑733576946
     [Google Scholar]
  32. LiuT. WeiQ. JinJ. LuoQ. LiuY. YangY. ChengC. LiL. PiJ. SiY. XiaoH. LiL. RaoS. WangF. YuJ. YuJ. ZouD. YiP. The m6A reader YTHDF1 promotes ovarian cancer progression via augmenting EIF3C translation.Nucleic Acids Res.20204873816383110.1093/nar/gkaa04831996915
     [Google Scholar]
  33. SinghM.S. RamishettiS. Landesman-MiloD. GoldsmithM. ChatterjeeS. PalakuriR. PeerD. Therapeutic gene silencing using targeted lipid nanoparticles in metastatic ovarian cancer.Small20211719210028710.1002/smll.20210028733825318
     [Google Scholar]
  34. DingX. HouL. ZhangH. ChenZ. LiuZ. GongJ. TangZ. HuR. EIF3C promotes lung cancer tumorigenesis by regulating the APP/HSPA1A/LMNB1 axis.Dis. Markers2022202211110.1155/2022/946409436157221
     [Google Scholar]
  35. LiuH. QinY. ZhouN. MaD. WangY. ZNF280A promotes lung adenocarcinoma development by regulating the expression of EIF3C.Cell Death Dis.20211213910.1038/s41419‑020‑03309‑933414445
     [Google Scholar]
  36. SemczukA. GogaczM. Semczuk-SikoraA. JóźwikM. RechbergerT. The putative role of TP53 alterations and p53 expression in borderline ovarian tumors - Correlation with clinicopathological features and prognosis: A mini-review.J. Cancer20178142684269110.7150/jca.1969128928856
     [Google Scholar]
  37. LevineA.J. p53: 800 million years of evolution and 40 years of discovery.Nat. Rev. Cancer202020847148010.1038/s41568‑020‑0262‑132404993
     [Google Scholar]
  38. BykovV.J.N. ErikssonS.E. BianchiJ. WimanK.G. Targeting mutant p53 for efficient cancer therapy.Nat. Rev. Cancer20181828910210.1038/nrc.2017.10929242642
     [Google Scholar]
  39. ZhangY. LozanoG. p53: Multiple facets of a rubik’s cube.Annu. Rev. Cancer Biol.20171118520110.1146/annurev‑cancerbio‑050216‑12192630775651
     [Google Scholar]
  40. KangH.J. RosenwaksZ. p53 and reproduction.Fertil. Steril.20181091394310.1016/j.fertnstert.2017.11.02629307398
     [Google Scholar]
  41. BoutelleA.M. AttardiL.D. p53 and tumor suppression: It takes a network.Trends Cell Biol.202131429831010.1016/j.tcb.2020.12.01133518400
     [Google Scholar]
  42. KandothC. McLellanM.D. VandinF. YeK. NiuB. LuC. XieM. ZhangQ. McMichaelJ.F. WyczalkowskiM.A. LeisersonM.D.M. MillerC.A. WelchJ.S. WalterM.J. WendlM.C. LeyT.J. WilsonR.K. RaphaelB.J. DingL. Mutational landscape and significance across 12 major cancer types.Nature2013502747133333910.1038/nature1263424132290
     [Google Scholar]
/content/journals/pra/10.2174/0115748928292248240401051408
Loading
Eukaryotic Initiation Factor 3C Can Affect the Proliferation and Invasion of Ovarian Cancer by Regulating the p53 Signalling Pathway
Recent Patents on Anti-Cancer Drug Discovery 20, 577 (2025); https://doi.org/10.2174/0115748928292248240401051408
/content/journals/pra/10.2174/0115748928292248240401051408
/content/journals/pra/10.2174/0115748928292248240401051408
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher’s website along with the published article.

file format download Download

  • Article Type:     Research Article
Keyword(s): Eukaryotic initiation factor 3C; gynecological cancers; invasion; oncology; ovarian cancer; p53 signalling pathway; proliferation

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test