Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Medicinal Chemistry
  4. Volume 32, Issue 8
  5. Article
Volume 32, Issue 8
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X
file format pdf download PDF
file format text download EPUB
side by side viewer icon HTML

Abstract

Background

The prognosis and survival rate of patients with head and neck squamous cell carcinoma (HNSCC) remain a serious public health concern. Therefore, elucidation of the underlying mechanisms responsible for the biological behavior of HNSCC is crucial for the development of effective treatment strategies.

Materials and Methods

In this study, we analyzed TCGA database and found that MAPK12 was overexpressed in tumor samples compared to normal samples, which was confirmed by microarray expression profiles, quantitative real-time polymerase chain reaction, and immunohistochemistry.

Results

Cell functional experiments, including the cell counting kit-8 assay, wound healing test, and transwell assay, revealed that MAPK12 overexpression increased the proliferation, invasion, and migration of HNSCC cells. A correlation was observed between MAPK12 expression and patient survival in HNSCC across several clinicopathological variables, including disease grade and stage. Analysis of immune-related functions demonstrated that HNSCC patients with low MAPK12 expression had a more favorable tumor immune microenvironment and better immunological functions.

Conclusion

Collectively, our study identified for the first time that MAPK12 is upregulated in HNSCC, functioning as an oncogene, indicating a suppressive tumor immune microenvironment and poor prognosis since it could promote cancer cell proliferation, invasion, and migration. However, further studies are needed to gain a more comprehensive understanding of the role of MAPK12 in HNSCC and other tumor types.

© 2025 Bentham Science Publishers
© 2025 The Author(s). Published by Bentham Science Publishers. This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
Loading

Article metrics loading...

/content/journals/cmc/10.2174/0109298673264903231107151241
2023-11-22
2025-04-11

  • From This Site

    /content/journals/cmc/10.2174/0109298673264903231107151241
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
The full text of this item is not currently available.

References

  1. LeelahavanichkulK. AmornphimolthamP. MolinoloA.A. BasileJ.R. KoontongkaewS. GutkindJ.S. A role for p38 MAPK in head and neck cancer cell growth and tumor-induced angiogenesis and lymphangiogenesis.Mol. Oncol.20148110511810.1016/j.molonc.2013.10.00324216180
     [Google Scholar]
  2. HuangP. HanJ. HuiL. MAPK signaling in inflammation-associated cancer development.Protein Cell20101321822610.1007/s13238‑010‑0019‑921203968
     [Google Scholar]
  3. JohnsonD.E. BurtnessB. LeemansC.R. LuiV.W.Y. BaumanJ.E. GrandisJ.R. Head and neck squamous cell carcinoma.Nat. Rev. Dis. Primers2020619210.1038/s41572‑020‑00224‑333243986
     [Google Scholar]
  4. SzturzP. Van LaerC. SimonC. Van GestelD. BourhisJ. VermorkenJ.B. Follow-up of head and neck cancer survivors: Tipping the balance of intensity.Front. Oncol.20201068810.3389/fonc.2020.0068832435619
     [Google Scholar]
  5. GuoY.J. PanW.W. LiuS.B. ShenZ.F. XuY. HuL.L. ERK/MAPK signalling pathway and tumorigenesis.Exp. Ther. Med.20201931997200732104259
     [Google Scholar]
  6. MoonH. RoS.W. MAPK/ERK signaling pathway in hepatocellular carcinoma.Cancers20211312302610.3390/cancers1312302634204242
     [Google Scholar]
  7. WeiJ. LiuR. HuX. LiangT. ZhouZ. HuangZ. MAPK signaling pathway-targeted marine compounds in cancer therapy.J. Cancer Res. Clin. Oncol.2021147132210.1007/s00432‑020‑03460‑y33389079
     [Google Scholar]
  8. AguzziA. MaggioniD. NicoliniG. TrediciG. GainiR.M. GaravelloW. MAP kinase modulation in squamous cell carcinoma of the oral cavity.Anticancer Res.200929130330819331166
     [Google Scholar]
  9. MarconiG.D. Della RoccaY. FonticoliL. MelfiF. RajanT.S. CarradoriS. PizzicannellaJ. TrubianiO. DiomedeF. C-Myc expression in oral squamous cell carcinoma: Molecular mechanisms in cell survival and cancer progression.Pharmaceuticals202215789010.3390/ph1507089035890188
     [Google Scholar]
  10. CargnelloM. RouxP.P. Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases.Microbiol. Mol. Biol. Rev.2011751508310.1128/MMBR.00031‑1021372320
     [Google Scholar]
  11. WangF. QiX.M. WertzR. MortensenM. HagenC. EvansJ. SheininY. JamesM. LiuP. TsaiS. ThomasJ. MackinnonA. DwinellM. MyersC.R. Bartrons BachR. FuL. ChenG. p38γ MAPK is essential for aerobic glycolysis and pancreatic tumorigenesis.Cancer Res.202080163251326410.1158/0008‑5472.CAN‑19‑328132580961
     [Google Scholar]
  12. LoeschM. ZhiH.Y. HouS.W. QiX.M. LiR.S. BasirZ. IftnerT. CuendaA. ChenG. p38γ MAPK cooperates with c-jun in trans-activating matrix metalloproteinase 9.J. Biol. Chem.201028520151491515810.1074/jbc.M110.10542920231272
     [Google Scholar]
  13. FangX. TangZ. ZhangH. QuanH. Long non-coding RNA DNM3OS/miR-204-5p/HIP1 axis modulates oral cancer cell viability and migration.J. Oral Pathol. Med.202049986587510.1111/jop.1304732463958
     [Google Scholar]
  14. YoshiharaK. ShahmoradgoliM. MartínezE. VegesnaR. KimH. Torres-GarciaW. TreviñoV. ShenH. LairdP.W. LevineD.A. CarterS.L. GetzG. Stemke-HaleK. MillsG.B. VerhaakR.G.W. Inferring tumour purity and stromal and immune cell admixture from expression data.Nat. Commun.201341261210.1038/ncomms361224113773
     [Google Scholar]
  15. ChenB. KhodadoustM.S. LiuC.L. NewmanA.M. AlizadehA.A. Profiling tumor infiltrating immune cells with CIBERSORT.Methods Mol. Biol.2018171124325910.1007/978‑1‑4939‑7493‑1_1229344893
     [Google Scholar]
  16. GeeleherP. CoxN. HuangR.S. pRRophetic: An R package for prediction of clinical chemotherapeutic response from tumor gene expression levels.PLoS One201499e10746810.1371/journal.pone.010746825229481
     [Google Scholar]
  17. RitchieM.E. PhipsonB. WuD. HuY. LawC.W. ShiW. SmythG.K. limma powers differential expression analyses for RNA-sequencing and microarray studies.Nucleic Acids Res.2015437e4710.1093/nar/gkv00725605792
     [Google Scholar]
  18. GuZ. EilsR. SchlesnerM. Complex heatmaps reveal patterns and correlations in multidimensional genomic data.Bioinformatics201632182847284910.1093/bioinformatics/btw31327207943
     [Google Scholar]
  19. GuZ. GuL. EilsR. SchlesnerM. BrorsB. Circlize implements and enhances circular visualization in R.Bioinformatics201430192811281210.1093/bioinformatics/btu39324930139
     [Google Scholar]
  20. WuT. HuE. XuS. ChenM. GuoP. DaiZ. FengT. ZhouL. TangW. ZhanL. FuX. LiuS. BoX. YuG. clusterprofiler 4.0: A universal enrichment tool for interpreting omics data.Innovation20212310014110.1016/j.xinn.2021.10014134557778
     [Google Scholar]
  21. WickhamH. Reshaping Data with the reshape Package.J. Stat. Softw.2007211212010.18637/jss.v021.i12
     [Google Scholar]
  22. QiX. TangJ. LoeschM. PohlN. AlkanS. ChenG. p38gamma mitogen-activated protein kinase integrates signaling crosstalk between Ras and estrogen receptor to increase breast cancer invasion.Cancer Res.200666157540754710.1158/0008‑5472.CAN‑05‑463916885352
     [Google Scholar]
  23. RosenthalD.T. IyerH. EscuderoS. BaoL. WuZ. VenturaA.C. KleerC.G. ArrudaE.M. GarikipatiK. MerajverS.D. p38γ promotes breast cancer cell motility and metastasis through regulation of RhoC GTPase, cytoskeletal architecture, and a novel leading edge behavior.Cancer Res.201171206338634910.1158/0008‑5472.CAN‑11‑129121862636
     [Google Scholar]
  24. ChenX.F. PanY. ZhengB. LuQ. p38gamma overexpression promotes renal cell carcinoma cell growth, proliferation and migration.Biochem. Biophys. Res. Commun.2019516246647310.1016/j.bbrc.2019.06.05631229268
     [Google Scholar]
  25. Tomás-LobaA. ManieriE. González-TeránB. MoraA. Leiva-VegaL. SantamansA.M. Romero-BecerraR. RodríguezE. Pintor-ChocanoA. FeixasF. LópezJ.A. CaballeroB. TrakalaM. BlancoÓ. TorresJ.L. Hernández-CosidoL. Montalvo-RomeralV. MatesanzN. Roche-MolinaM. BernalJ.A. MischoH. LeónM. CaballeroA. Miranda-SaavedraD. Ruiz-CabelloJ. NevzorovaY.A. CuberoF.J. BravoJ. VázquezJ. MalumbresM. MarcosM. OsunaS. SabioG. p38γ is essential for cell cycle progression and liver tumorigenesis.Nature2019568775355756010.1038/s41586‑019‑1112‑830971822
     [Google Scholar]
  26. SuC. SunQ. LiuS. WangH. FengL. CaoY. Targeting p38γ to inhibit human colorectal cancer cell progression.Biochem. Biophys. Res. Commun.2019517117217910.1016/j.bbrc.2019.07.03831349971
     [Google Scholar]
  27. XuW. LiuR. DaiY. HongS. DongH. WangH. The role of p38γ in cancer: From review to outlook.Int. J. Biol. Sci.202117144036404610.7150/ijbs.6353734671218
     [Google Scholar]
  28. YinD.P. ZhengY.F. SunP. YaoM.Y. XieL. DouX.W. TianY. LiuJ.S. The pro-tumorigenic activity of p38γ overexpression in nasopharyngeal carcinoma.Cell Death Dis.202213321010.1038/s41419‑022‑04637‑835246508
     [Google Scholar]
  29. LiY. TangX. HeQ. YangX. RenX. WenX. ZhangJ. WangY. LiuN. MaJ. Overexpression of mitochondria mediator gene TRIAP1 by miR-320b loss is associated with progression in nasopharyngeal carcinoma.PLoS Genet.2016127e100618310.1371/journal.pgen.100618327428374
     [Google Scholar]
  30. WangS. WangA. ZhangY. ZhuK. WangX. ChenY. WuJ. The role of MAPK11/12/13/14 (p38 MAPK) protein in dopamine agonist-resistant prolactinomas.BMC Endocr. Disord.202121123510.1186/s12902‑021‑00900‑934814904
     [Google Scholar]
  31. EslamiA. MiyaguchiK. MogushiK. WatanabeH. OkadaN. ShibuyaH. MizushimaH. MiuraM. TanakaH. PARVB overexpression increases cell migration capability and defines high risk for endophytic growth and metastasis in tongue squamous cell carcinoma.Br. J. Cancer2015112233834410.1038/bjc.2014.59025422907
     [Google Scholar]
  32. WuJ.B. LiX.J. LiuH. LiuX.P. Ring finger protein 215 is a potential prognostic biomarker involved in immune infiltration and angiogenesis in colorectal cancer.Biomed. Rep.20231915010.3892/br.2023.163337383678
     [Google Scholar]
  33. LiuL. LuoC. LuoY. ChenL. LiuY. WangY. HanJ. ZhangY. WeiN. XieZ. WuW. WuG. FengY. MRPL33 and its splicing regulator hnRNPK are required for mitochondria function and implicated in tumor progression.Oncogene2018371869410.1038/onc.2017.31428869607
     [Google Scholar]
  34. WangJ. SongZ. RenL. ZhangB. ZhangY. YangX. LiuT. GuY. FengC. Pan-cancer analysis supports MAPK12 as a potential prognostic and immunotherapeutic target in multiple tumor types, including in THCA.Oncol. Lett.202224644510.3892/ol.2022.1356536420075
     [Google Scholar]
/content/journals/cmc/10.2174/0109298673264903231107151241
Loading
The Novel Prognostic Biomarker MAPK12 Promotes Migration, Proliferation, and Invasion in Head and Neck Squamous Cell Carcinoma
Curr. Med. Chem. 32, 1621 (2025); https://doi.org/10.2174/0109298673264903231107151241
/content/journals/cmc/10.2174/0109298673264903231107151241
/content/journals/cmc/10.2174/0109298673264903231107151241
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): biological behavior; Head and neck squamous cell carcinoma; immune infiltration; MAPK superfamily; MAPK12; oral squamous cell carcinoma; tumor immune microenvironment; tumor microenvironment

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