Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Pharmaceutical Biotechnology
  4. Volume 26, Issue 1
  5. Article
Volume 26, Issue 1
  • ISSN: 1389-2010
  • E-ISSN: 1873-4316

Abstract

Background

Breast Cancer (BC) is a female malignancy with a high mortality rate. Novel diagnostic and prognostic biomarkers are valuable for reducing BC mortality. Our study is designed to undrape the precise role of the LINC00466/miR-4731-5p/EPHA2 axis in BC.

Methods

The Cancer Genome Atlas (TCGA) sequencing dataset was utilized to compare the levels of LINC00466. The levels of LINC00466, miR-4731-5p, and EPHA2 were tested by qRT-PCR. Cell proliferation and cycle were detected by CCK-8 assay and flow cytometer. role of LINC00466 was tested by Xenograft nude models. Binding sites were predicted by TargetScan and Starbase. The binding relationship was employed by Dual-luciferase reporter gene assay and RNA pull-down assay.

Results

LINC00466 was increased in human breast cancer tissues. LINC00466 was negatively associated with miR-4731-5p and positively correlated with EPHA2 in human breast cancer tissues. Down-regulation of LINC00466 suppressed the proliferation and arrested the cell cycle of breast cancer cells, and inhibited tumor growth .

Conclusion

LINC00466 promoted BC development mediating the miR-4731-5p/EPHA2 axis, which has the potential value as a promising therapeutic target in BC.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cpb/10.2174/0113892010290582240419051056
2024-05-09
2024-12-28

  • From This Site

    /content/journals/cpb/10.2174/0113892010290582240419051056
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. TorreL.A. BrayF. SiegelR.L. FerlayJ. Lortet-TieulentJ. JemalA. Global cancer statistics, 2012.CA Cancer J. Clin.20156528710810.3322/caac.21262 25651787
     [Google Scholar]
  2. BrayF. FerlayJ. SoerjomataramI. SiegelR.L. TorreL.A. JemalA. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J. Clin.201868639442410.3322/caac.21492 30207593
     [Google Scholar]
  3. AichM. ChakrabortyD. Role of lncRNAs in stem cell maintenance and differentiation.Curr. Top. Dev. Biol.20201387311210.1016/bs.ctdb.2019.11.003 32220299
     [Google Scholar]
  4. RazaviH. KatanforoshA. Identification of novel key regulatory lncRNAs in gastric adenocarcinoma.BMC Genomics202223135210.1186/s12864‑022‑08578‑6 35525925
     [Google Scholar]
  5. BhanA. SoleimaniM. MandalS.S. Long noncoding RNA and cancer: A new paradigm.Cancer Res.201777153965398110.1158/0008‑5472.CAN‑16‑2634 28701486
     [Google Scholar]
  6. FernandoT.R. ContrerasJ.R. ZampiniM. Rodriguez-MalaveN.I. AlbertiM.O. AnguianoJ. TranT.M. PalanichamyJ.K. GajetonJ. UngN.M. ArosC.J. WatersE.V. CaseroD. BassoG. PigazziM. RaoD.S. The lncRNA CASC15 regulates SOX4 expression in RUNX1-rearranged acute leukemia.Mol. Cancer201716112610.1186/s12943‑017‑0692‑x 28724437
     [Google Scholar]
  7. RynkevicieneR. SimieneJ. StrainieneE. StankeviciusV. UsinskieneJ. Miseikyte KaubrieneE. MeskinyteI. CicenasJ. SuziedelisK. Non-coding RNAs in glioma.Cancers20181111710.3390/cancers11010017 30583549
     [Google Scholar]
  8. WangC. ChenL. YangY. ZhangM. WongG. Identification of bladder cancer prognostic biomarkers using an ageing gene-related competitive endogenous RNA network.Oncotarget201786711174211175310.18632/oncotarget.22905 29340088
     [Google Scholar]
  9. WuQ. XiangS. MaJ. HuiP. WangT. MengW. ShiM. WangY. Long non‐coding RNA CASC 15 regulates gastric cancer cell proliferation, migration and epithelial mesenchymal transition by targeting CDKN 1A and ZEB 1.Mol. Oncol.201812679981310.1002/1878‑0261.12187 29489064
     [Google Scholar]
  10. YaoK. WangQ. JiaJ. ZhaoH. A competing endogenous RNA network identifies novel mRNA, miRNA and lncRNA markers for the prognosis of diabetic pancreatic cancer.Tumour Biol.201739610.1177/1010428317707882 28639886
     [Google Scholar]
  11. LiZ. XieX. FanX. LiX. Long non-coding RNA MINCR regulates miR-876-5p/GSPT1 axis to aggravate glioma progression.Neurochem. Res.20204571690169910.1007/s11064‑020‑03029‑8 32333234
     [Google Scholar]
  12. DongH.X. WangR. JinX.Y. ZengJ. PanJ. LncRNA DGCR5 promotes lung adenocarcinoma (LUAD) progression via inhibiting hsa‐mir‐22‐3p.J. Cell. Physiol.201823354126413610.1002/jcp.26215 29030962
     [Google Scholar]
  13. YuanS. LiuQ. HuZ. ZhouZ. WangG. LiC. XieW. MengG. XiangY. WuN. WuL. YuZ. BaiL. LiY. Long non-coding RNA MUC5B-AS1 promotes metastasis through mutually regulating MUC5B expression in lung adenocarcinoma.Cell Death Dis.20189545010.1038/s41419‑018‑0472‑6 29670111
     [Google Scholar]
  14. BianZ. ZhouM. CuiK. YangF. CaoY. SunS. LiuB. GongL. LiJ. WangX. LiC. YaoS. YinY. HuangS. FeiB. HuangZ. SNHG17 promotes colorectal tumorigenesis and metastasis via regulating Trim23-PES1 axis and miR-339-5p-FOSL2-SNHG17 positive feedback loop.J. Exp. Clin. Cancer Res.202140136010.1186/s13046‑021‑02162‑8 34782005
     [Google Scholar]
  15. TamC. WongJ.H. TsuiS.K.W. ZuoT. ChanT.F. NgT.B. LncRNAs with miRNAs in regulation of gastric, liver, and colorectal cancers: Updates in recent years.Appl. Microbiol. Biotechnol.2019103124649467710.1007/s00253‑019‑09837‑5 31062053
     [Google Scholar]
  16. HuangL. LiX. YeH. LiuY. LiangX. YangC. HuaL. YanZ. ZhangX. Long non-coding RNA NCK1-AS1 promotes the tumorigenesis of glioma through sponging microRNA-138-2-3p and activating the TRIM24/Wnt/β-catenin axis.J. Exp. Clin. Cancer Res.20203916310.1186/s13046‑020‑01567‑1 32293515
     [Google Scholar]
  17. ZhaoM. ShaoY. XuJ. ZhangB. LiC. GongJ. LINC00466 impacts cell proliferation, metastasis and sensitivity to temozolomide of glioma by sponging miR-137 to regulate PPP1R14B expression.OncoTargets Ther.2021141147115910.2147/OTT.S273264 33642868
     [Google Scholar]
  18. MaT. HuY. GuoY. YanB. Tumor-promoting activity of long noncoding RNA LINC00466 in lung adenocarcinoma viamiR-144-regulated HOXA10 axis.Am. J. Pathol.2019189112154217010.1016/j.ajpath.2019.06.014 31381886
     [Google Scholar]
  19. GebertL.F.R. MacRaeI.J. Regulation of microRNA function in animals.Nat. Rev. Mol. Cell Biol.2019201213710.1038/s41580‑018‑0045‑7 30108335
     [Google Scholar]
  20. NaeliP. WinterT. HackettA.P. AlboushiL. JafarnejadS.M. The intricate balance between microRNA‐induced mRNA decay and translational repression.FEBS J.2023290102508252410.1111/febs.16422 35247033
     [Google Scholar]
  21. XuK. HanB. BaiY. MaX.Y. JiZ.N. XiongY. MiaoS.K. ZhangY.Y. ZhouL.M. MiR-451a suppressing BAP31 can inhibit proliferation and increase apoptosis through inducing ER stress in colorectal cancer.Cell Death Dis.201910315210.1038/s41419‑019‑1403‑x 30770794
     [Google Scholar]
  22. WilsonK. ShiuanE. Brantley-SiedersD.M. Oncogenic functions and therapeutic targeting of EphA2 in cancer.Oncogene202140142483249510.1038/s41388‑021‑01714‑8 33686241
     [Google Scholar]
  23. ZhaoP. SunJ. HuangX. ZhangX. LiuX. LiuR. DuG. GanW. YangC. TangY. ChenC. JiangD. Targeting the KLF5-EphA2 axis can restrain cancer stemness and overcome chemoresistance in basal-like breast cancer.Int. J. Biol. Sci.20231961861187410.7150/ijbs.82567 37063424
     [Google Scholar]
  24. ZhouY. OkiR. TanakaA. SongL. TakashimaA. HamadaN. YokoyamaS. YanoS. SakuraiH. Cellular stress induces non-canonical activation of the receptor tyrosine kinase EphA2 through the p38-MK2-RSK signaling pathway.J. Biol. Chem.2023299510469910.1016/j.jbc.2023.104699 37059179
     [Google Scholar]
  25. KroenkeC.H. MichaelY.L. PooleE.M. KwanM.L. NechutaS. LeasE. CaanB.J. PierceJ. ShuX.O. ZhengY. ChenW.Y. Postdiagnosis social networks and breast cancer mortality in the after breast cancer pooling project.Cancer201712371228123710.1002/cncr.30440 27943274
     [Google Scholar]
  26. ShanY. MaJ. PanY. HuJ. LiuB. JiaL. LncRNA SNHG7 sponges miR-216b to promote proliferation and liver metastasis of colorectal cancer through upregulating GALNT1.Cell Death Dis.20189772210.1038/s41419‑018‑0759‑7 29915311
     [Google Scholar]
  27. SunW. JiangC. JiY. XiaoC. SongH. Long noncoding RNAs: New regulators of resistance to systemic therapies for gastric cancer.BioMed Res. Int.2021202111410.1155/2021/8853269 33506041
     [Google Scholar]
  28. ZhaoL. SunH. KongH. ChenZ. ChenB. ZhouM. ZhouM. The Lncrna-TUG1/EZH2 axis promotes pancreatic cancer cell proliferation, migration and EMT phenotype formation through sponging Mir-382.Cell. Physiol. Biochem.20174262145215810.1159/000479990 28813705
     [Google Scholar]
  29. MaoY. LiuR. ZhouH. YinS. ZhaoQ. DingX. WangH. Transcriptome analysis of miRNA–lncRNA–mRNA interactions in the malignant transformation process of gastric cancer initiation.Cancer Gene Ther.201724626727510.1038/cgt.2017.14 28524153
     [Google Scholar]
  30. NohJ.H. KimK.M. McCluskyW.G. AbdelmohsenK. GorospeM. Cytoplasmic functions of long noncoding RNAs.Wiley Interdiscip. Rev. RNA201893e147110.1002/wrna.1471 29516680
     [Google Scholar]
  31. MengQ. LiuM. ChengR. LINC00461/miR-4478/E2F1 feedback loop promotes non-small cell lung cancer cell proliferation and migration.Biosci. Rep.2020402BSR2019134510.1042/BSR20191345 31934717
     [Google Scholar]
  32. HouJ. WangY. ZhangH. HuY. XinX. LiX. Silencing of LINC00461 enhances radiosensitivity of lung adenocarcinoma cells by down‐regulating HOXA10 via microRNA‐195.J. Cell. Mol. Med.20202452879289010.1111/jcmm.14859 31967713
     [Google Scholar]
  33. YaoY. ZhangT. QiL. LiuR. LiuG. WangX. LiJ. LiJ. SunC. Competitive endogenous RNA network construction and comparison of lung squamous cell carcinoma in smokers and nonsmokers.Dis. Markers2019201911410.1155/2019/5292787 31885738
     [Google Scholar]
  34. WangJ.J. HuangY.Q. SongW. LiY.F. WangH. WangW.J. HuangM. Comprehensive analysis of the lncRNA associated competing endogenous RNA network in breast cancer.Oncol. Rep.20194262572258210.3892/or.2019.7374 31638237
     [Google Scholar]
  35. GaoC. LiH. ZhuangJ. ZhangH. WangK. YangJ. LiuC. LiuL. ZhouC. SunC. The construction and analysis of ceRNA networks in invasive breast cancer: A study based on The Cancer Genome Atlas.Cancer Manag. Res.20181111110.2147/CMAR.S182521 30588106
     [Google Scholar]
  36. DebnathT. Deb NathN.C. KimE.K. LeeK.G. Role of phytochemicals in the modulation of miRNA expression in cancer.Food Funct.20178103432344210.1039/C7FO00739F 28782785
     [Google Scholar]
  37. LiuC. LiuR. ZhangD. DengQ. LiuB. ChaoH.P. RycajK. TakataY. LinK. LuY. ZhongY. KrolewskiJ. ShenJ. TangD.G. MicroRNA-141 suppresses prostate cancer stem cells and metastasis by targeting a cohort of pro-metastasis genes.Nat. Commun.2017811427010.1038/ncomms14270 28112170
     [Google Scholar]
  38. IngenitoF. RoscignoG. AffinitoA. NuzzoS. ScognamiglioI. QuintavalleC. CondorelliG. The role of Exo-miRNAs in cancer: A focus on therapeutic and diagnostic applications.Int. J. Mol. Sci.20192019468710.3390/ijms20194687 31546654
     [Google Scholar]
  39. YamamuraS. Imai-SumidaM. TanakaY. DahiyaR. Interaction and cross-talk between non-coding RNAs.Cell. Mol. Life Sci.201875346748410.1007/s00018‑017‑2626‑6 28840253
     [Google Scholar]
  40. YanZ. ZhangW. XiongY. WangY. LiZ. Long noncoding RNA FLVCR1-AS1 aggravates biological behaviors of glioma cells via targeting miR-4731-5p/E2F2 axis.Biochem. Biophys. Res. Commun.2020521371672010.1016/j.bbrc.2019.10.106 31699367
     [Google Scholar]
  41. IshigakiH. MinamiT. MorimuraO. KitaiH. HorioD. KodaY. FujimotoE. NegiY. NakajimaY. NikiM. KanemuraS. ShibataE. MikamiK. TakahashiR. YokoiT. KuribayashiK. KijimaT. EphA2 inhibition suppresses proliferation of small-cell lung cancer cells through inducing cell cycle arrest.Biochem. Biophys. Res. Commun.2019519484685310.1016/j.bbrc.2019.09.076 31558317
     [Google Scholar]
/content/journals/cpb/10.2174/0113892010290582240419051056
Loading
LncRNA LINC00466 Promotes the Progression of Breast Cancer via miR-4731-5p/EPHA2 Pathway
Current Pharmaceutical Biotechnology 26, 120 (2025); https://doi.org/10.2174/0113892010290582240419051056
/content/journals/cpb/10.2174/0113892010290582240419051056
/content/journals/cpb/10.2174/0113892010290582240419051056
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): biomarkers; Breast cancer; EPHA2; LINC00466; miR-4731-5p; Xenograft nude models

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