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2000
Volume 25, Issue 10
  • ISSN: 1568-0096
  • E-ISSN: 1873-5576

Abstract

Objective

This study aimed to analyze the expression of Matrix Metalloproteinase 7 (MMP7) and molecular mechanism at the Transcription Factor (TF) level in Oral Squamous Cell Carcinoma (OSCC).

Methods

MMP7 expression was preliminarily explored in Head and Neck Squamous Cell Carcinoma (HNSCC) in the online database, followed by functional analysis and prediction of TF of MMP7. IHC was employed to detect MMP7 levels in OSCC samples. SCC9 and 293T cells were used to explore the transcriptional and regulatory effects of predicted TF on MMP7 by reporter double luciferase assay, RT-qPCR, western blotting, and cellular immunofluorescence. Transwell and TUNEL were employed to detect the migration and apoptosis.

Results

MMP7 was significantly up-regulated in HNSCC and OSCC tissues. Moreover, MMP7 was positively correlated with CAFs and significantly enriched in the signaling pathway of RNA degradation. The c-Jun pathway was also up-regulated in OSCC tissues, and predicted to be optimal TF of MMP7 with positive regulatory relationship. In OSCC, silencing and over-expression of c-Jun significantly decreased and increased the level of MMP7. Meanwhile, c-Jun affected the behavior of SCC9 cells, which showed that after c-Jun gene silencing, the ability of cell migration was weakened, while apoptosis was enhanced. When c-Jun gene was overexpressed, the migration ability was enhanced, but apoptosis was not significantly affected.

Conclusion

MMP7 has been proven to be a key protein in the development of OSCC, and has the potential to become a biological marker and therapeutic target. It has been found that c-Jun could bind to the MMP7 promoter region, and the silencing or overexpression of c-Jun can positively regulate the expression of MMP7.

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References

  1. SungH. FerlayJ. SiegelR.L. Global cancer statistics 2020: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J. Clin.202171320924910.3322/caac.2166033538338
    [Google Scholar]
  2. SasahiraT. KiritaT. Hallmarks of cancer-related newly prognostic factors of oral squamous cell carcinoma.Int. J. Mol. Sci.2018198241310.3390/ijms1908241330115834
    [Google Scholar]
  3. PekarekL. Garrido-GilM. Sánchez-CendraA. Emerging histological and serological biomarkers in oral squamous cell carcinoma: Applications in diagnosis, prognosis evaluation and personalized therapeutics (Review).Oncol. Rep.202350621310.3892/or.2023.865037859591
    [Google Scholar]
  4. PanareseI. AquinoG. RonchiA. Oral and Oropharyngeal squamous cell carcinoma: prognostic and predictive parameters in the etiopathogenetic route.Expert Rev. Anticancer Ther.201919210511910.1080/14737140.2019.156128830582397
    [Google Scholar]
  5. HasegawaK. FujiiS. MatsumotoS. TajiriY. KikuchiA. KiyoshimaT. YAP signaling induces PIEZO1 to promote oral squamous cell carcinoma cell proliferation.J. Pathol.20212531809310.1002/path.555332985688
    [Google Scholar]
  6. FanT. WangX. ZhangS. NUPR1 promotes the proliferation and metastasis of oral squamous cell carcinoma cells by activating TFE3-dependent autophagy.Signal Transduct. Target. Ther.20227113010.1038/s41392‑022‑00939‑735462576
    [Google Scholar]
  7. PengQ.S. ChengY.N. ZhangW.B. FanH. MaoQ.H. XuP. circRNA_0000140 suppresses oral squamous cell carcinoma growth and metastasis by targeting miR-31 to inhibit Hippo signaling pathway.Cell Death Dis.202011211210.1038/s41419‑020‑2273‑y32041942
    [Google Scholar]
  8. QieY. SunX. YangY. YanT. Emerging functions and applications of exosomes in oral squamous cell carcinoma.J. Oral Pathol. Med.2023521088689410.1111/jop.1347937701945
    [Google Scholar]
  9. WarnakulasuriyaS. Global epidemiology of oral and oropharyngeal cancer.Oral Oncol.2009454-530931610.1016/j.oraloncology.2008.06.00218804401
    [Google Scholar]
  10. PanzarellaV. PizzoG. CalvinoF. CompilatoD. ColellaG. CampisiG. Diagnostic delay in oral squamous cell carcinoma: the role of cognitive and psychological variables.Int. J. Oral Sci.201461394510.1038/ijos.2013.8824287962
    [Google Scholar]
  11. LingZ. ChengB. TaoX. Epithelial‐to‐mesenchymal transition in oral squamous cell carcinoma: Challenges and opportunities.Int. J. Cancer202114871548156110.1002/ijc.3335233091960
    [Google Scholar]
  12. DanH. LiuS. LiuJ. RACK1 promotes cancer progression by increasing the M2/M1 macrophage ratio via the NF‐κB pathway in oral squamous cell carcinoma.Mol. Oncol.202014479580710.1002/1878‑0261.1264431997535
    [Google Scholar]
  13. LuY. ZhengZ. YuanY. The emerging role of exosomes in oral squamous cell carcinoma.Front. Cell Dev. Biol.2021962810310.3389/fcell.2021.62810333718365
    [Google Scholar]
  14. SHahinasJ. HysiD. Methods and risk of bias in molecular marker prognosis studies in oral squamous cell carcinoma.Oral Dis.2018241-211511910.1111/odi.1275329480595
    [Google Scholar]
  15. JiangM. LiB. STAT3 and its targeting inhibitors in oral squamous cell carcinoma.Cells20221119313110.3390/cells1119313136231093
    [Google Scholar]
  16. ZanoniD.K. MonteroP.H. MigliacciJ.C. Survival outcomes after treatment of cancer of the oral cavity (1985–2015).Oral Oncol.20199011512110.1016/j.oraloncology.2019.02.00130846169
    [Google Scholar]
  17. ImpolaU. CuccuruM.A. MasalaM.V. JeskanenL. CottoniF. Saarialho-KereU. Preliminary communication: matrix metalloproteinases in Kaposi’s sarcoma.Br. J. Dermatol.2003149490590710.1046/j.1365‑2133.2003.05561.x14616400
    [Google Scholar]
  18. ImpolaU. TorisevaM. SuomelaS. Matrix metalloproteinase‐19 is expressed by proliferating epithelium but disappears with neoplastic dedifferentiation.Int. J. Cancer2003103670971610.1002/ijc.1090212516088
    [Google Scholar]
  19. EbleJ.A. NilandS. The extracellular matrix in tumor progression and metastasis.Clin. Exp. Metastasis201936317119810.1007/s10585‑019‑09966‑130972526
    [Google Scholar]
  20. MiguelA.F.P. MelloF.W. MeloG. RiveroE.R.C. Association between immunohistochemical expression of matrix metalloproteinases and metastasis in oral squamous cell carcinoma: Systematic review and meta‐analysis.Head Neck202042356958410.1002/hed.2600931750584
    [Google Scholar]
  21. CaiM. ZhengZ. BaiZ. Overexpression of angiogenic factors and matrix metalloproteinases in the saliva of oral squamous cell carcinoma patients: potential non-invasive diagnostic and therapeutic biomarkers.BMC Cancer202222153010.1186/s12885‑022‑09630‑035545767
    [Google Scholar]
  22. SaleemZ. ShaikhA.H. ZamanU. Estimation of salivary matrix metalloproteinases- 12 (MMP- 12) levels among patients presenting with oral submucous fibrosis and oral squamous cell carcinoma.BMC Oral Health202121120510.1186/s12903‑021‑01571‑733892690
    [Google Scholar]
  23. MoneaM. PopA.M. The use of salivary levels of matrix metalloproteinases as an adjuvant method in the early diagnosis of oral squamous cell carcinoma: a narrative literature review.Curr. Issues Mol. Biol.202244126306632210.3390/cimb4412043036547091
    [Google Scholar]
  24. de AlmeidaL.G.N. ThodeH. EslambolchiY. Matrix metalloproteinases: from molecular mechanisms to physiology, pathophysiology, and pharmacology.Pharmacol. Rev.202274371477010.1124/pharmrev.121.00034935738680
    [Google Scholar]
  25. BassiouniW. AliM.A.M. SchulzR. Multifunctional intracellular matrix metalloproteinases: implications in disease.FEBS J.2021288247162718210.1111/febs.1570133405316
    [Google Scholar]
  26. KleinerD.E. Stetler-StevensonW.G. Matrix metalloproteinases and metastasis.Cancer Chemother. Pharmacol.1999437S42S5110.1007/s00280005109710357558
    [Google Scholar]
  27. PittayapruekP. MeephansanJ. PrapapanO. KomineM. OhtsukiM. Role of matrix metalloproteinases in photoaging and photocarcinogenesis.Int. J. Mol. Sci.201617686810.3390/ijms1706086827271600
    [Google Scholar]
  28. VarinskaL. GalP. MojzisovaG. MirossayL. MojzisJ. Soy and breast cancer: focus on angiogenesis.Int. J. Mol. Sci.2015165117281174910.3390/ijms16051172826006245
    [Google Scholar]
  29. FrielingJ.S. LiT. TauroM. LynchC.C. Prostate cancer-derived MMP-3 controls intrinsic cell growth and extrinsic angiogenesis.Neoplasia2020221051152110.1016/j.neo.2020.08.00432896761
    [Google Scholar]
  30. WangX. ShiX. LuH. Succinylation inhibits the enzymatic hydrolysis of the extracellular matrix protein fibrillin 1 and promotes gastric cancer progression.Adv. Sci. (Weinh.)2022927220054610.1002/advs.20220054635901491
    [Google Scholar]
  31. MondalS. AdhikariN. BanerjeeS. AminS.A. JhaT. Matrix metalloproteinase-9 (MMP-9) and its inhibitors in cancer: A minireview.Eur. J. Med. Chem.202019411226010.1016/j.ejmech.2020.11226032224379
    [Google Scholar]
  32. RashidZ.A. BardaweelS.K. Novel matrix metalloproteinase-9 (mmp-9) inhibitors in cancer treatment.Int. J. Mol. Sci.202324151213310.3390/ijms24151213337569509
    [Google Scholar]
  33. SbardellaD. FasciglioneG.F. GioiaM. Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes.Mol. Aspects Med.201233211920810.1016/j.mam.2011.10.01522100792
    [Google Scholar]
  34. OuS. ChenH. WangH. Fusobacterium nucleatum upregulates MMP7 to promote metastasis-related characteristics of colorectal cancer cell via activating MAPK(JNK)-AP1 axis.J. Transl. Med.202321170410.1186/s12967‑023‑04527‑337814323
    [Google Scholar]
  35. YuanJ.Q. ZhangK.J. WangS.M. GuoL. YAP1/MMP7/CXCL16 axis affects efficacy of neoadjuvant chemotherapy via tumor environment immunosuppression in triple-negative breast cancer.Gland Surg.20211092799281410.21037/gs‑21‑61234733729
    [Google Scholar]
  36. NiuJ. LiX.M. WangX. DKK1 inhibits breast cancer cell migration and invasion through suppression of β-catenin/MMP7 signaling pathway.Cancer Cell Int.201919116810.1186/s12935‑019‑0883‑131285694
    [Google Scholar]
  37. VermaS.P. DasP. Monensin induces cell death by autophagy and inhibits matrix metalloproteinase 7 (MMP7) in UOK146 renal cell carcinoma cell line. In Vitro Cell. Dev. Biol. Anim.2018541073674210.1007/s11626‑018‑0298‑730324243
    [Google Scholar]
  38. GaireM. MagbanuaZ. McDonnellS. McNeilL. LovettD.H. MatrisianL.M. Structure and expression of the human gene for the matrix metalloproteinase matrilysin.J. Biol. Chem.199426932032204010.1016/S0021‑9258(17)42131‑48294454
    [Google Scholar]
  39. TanR.J. LiuY. Matrix metalloproteinases in kidney homeostasis and diseases.Am. J. Physiol. Renal Physiol.2012302111351136110.1152/ajprenal.00037.201222492945
    [Google Scholar]
  40. GobinE. BagwellK. WagnerJ. A pan-cancer perspective of matrix metalloproteases (MMP) gene expression profile and their diagnostic/prognostic potential.BMC Cancer201919158110.1186/s12885‑019‑5768‑031200666
    [Google Scholar]
  41. ChanB.Y.H. RoczkowskyA. ChoW.J. MMP inhibitors attenuate doxorubicin cardiotoxicity by preventing intracellular and extracellular matrix remodelling.Cardiovasc. Res.2021117118820010.1093/cvr/cvaa01731995179
    [Google Scholar]
  42. KessenbrockK. PlaksV. WerbZ. Matrix metalloproteinases: regulators of the tumor microenvironment.Cell20101411526710.1016/j.cell.2010.03.01520371345
    [Google Scholar]
  43. RamankulovA. LeinM. JohannsenM. SchraderM. MillerK. JungK. Plasma matrix metalloproteinase‐7 as a metastatic marker and survival predictor in patients with renal cell carcinomas.Cancer Sci.20089961188119410.1111/j.1349‑7006.2008.00802.x18422740
    [Google Scholar]
  44. XuY.W. ChenH. GuoH.P. Combined detection of serum autoantibodies as diagnostic biomarkers in esophagogastric junction adenocarcinoma.Gastric Cancer201922354655710.1007/s10120‑018‑0894‑y30426295
    [Google Scholar]
  45. Van DorenS.R. MMP-7 marks severe pancreatic cancer and alters tumor cell signaling by proteolytic release of ectodomains.Biochem. Soc. Trans.202250283985110.1042/BST2021064035343563
    [Google Scholar]
  46. LiuM. HuangL. LiuY. Identification of the MMP family as therapeutic targets and prognostic biomarkers in the microenvironment of head and neck squamous cell carcinoma.J. Transl. Med.202321120810.1186/s12967‑023‑04052‑336941602
    [Google Scholar]
  47. RezaeiF. ImaniM.M. Lopez-JornetP. SadeghiM. Estimation of serum and salivary matrix metalloproteinase levels in oral squamous cell carcinoma patients: a systematic review and meta-analysis.Postepy Dermatol. Alergol.202138110611410.5114/ada.2021.10428534408576
    [Google Scholar]
  48. Ahmed Haji OmarA. HaglundC. VirolainenS. MMP-7, MMP-8, and MMP-9 in oral and cutaneous squamous cell carcinomas.Oral Surg. Oral Med. Oral Pathol. Oral Radiol.2015119445946710.1016/j.oooo.2014.12.01925697929
    [Google Scholar]
  49. LiM. GaoF. YuX. Promotion of ubiquitination-dependent survivin destruction contributes to xanthohumol-mediated tumor suppression and overcomes radioresistance in human oral squamous cell carcinoma.J. Exp. Clin. Cancer Res.20203918810.1186/s13046‑020‑01593‑z
    [Google Scholar]
  50. JiangT. XieP. LiuH. Circulating anti–matrix metalloproteinase-7 antibodies may be a potential biomarker for oral squamous cell carcinoma.J. Oral Maxillofac. Surg.201674365065710.1016/j.joms.2015.09.01626454036
    [Google Scholar]
  51. De VicenteJ.C. Lequerica-FernándezP. SantamaríaJ. FresnoM.F. Expression of MMP‐7 and MT1‐MMP in oral squamous cell carcinoma as predictive indicator for tumor invasion and prognosis.J. Oral Pathol. Med.200736741542410.1111/j.1600‑0714.2007.00546.x17617835
    [Google Scholar]
  52. ZanconatoF. ForcatoM. BattilanaG. Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth.Nat. Cell Biol.20151791218122710.1038/ncb321626258633
    [Google Scholar]
  53. BakiriL. HasenfussS.C. Guío-CarriónA. ThomsenM.K. HasselblattP. WagnerE.F. Liver cancer development driven by the AP-1/c-Jun~Fra-2 dimer through c-Myc.Proc. Natl. Acad. Sci. USA202412118240418812110.1073/pnas.240418812138657045
    [Google Scholar]
  54. SongD. LianY. ZhangL. The potential of activator protein 1 (AP-1) in cancer targeted therapy.Front. Immunol.202314122489210.3389/fimmu.2023.122489237483616
    [Google Scholar]
  55. MirzaeiH. KhodadadN. KaramiC. PirmoradiR. KhanizadehS. The AP-1 pathway; A key regulator of cellular transformation modulated by oncogenic viruses.Rev. Med. Virol.20203012088
    [Google Scholar]
  56. JiaY. YanQ. ZhengY. Long non-coding RNA NEAT1 mediated RPRD1B stability facilitates fatty acid metabolism and lymph node metastasis via c-Jun/c-Fos/SREBP1 axis in gastric cancer.J. Exp. Clin. Cancer Res.202241128710.1186/s13046‑022‑02449‑436171622
    [Google Scholar]
  57. KarakaslarE.O. KatiyarN. HashamM. Transcriptional activation of Jun and Fos members of the AP‐1 complex is a conserved signature of immune aging that contributes to inflammaging.Aging Cell20232241379210.1111/acel.1379236840360
    [Google Scholar]
  58. BejjaniF. EvannoE. ZibaraK. PiechaczykM. Jariel-EncontreI. The AP-1 transcriptional complex: Local switch or remote command?Biochim. Biophys. Acta Rev. Cancer201918721112310.1016/j.bbcan.2019.04.00331034924
    [Google Scholar]
  59. HessJ. AngelP. Schorpp-KistnerM. AP-1 subunits: quarrel and harmony among siblings.J. Cell Sci.2004117255965597310.1242/jcs.0158915564374
    [Google Scholar]
  60. De SousaS.O.M. MesquitaR.A. PintoD.S.Jr GutkindS. Immunolocalization of c‐Fos and c‐Jun in human oral mucosa and in oral squamous cell carcinoma.J. Oral Pathol. Med.2002312788110.1046/j.0904‑2512.2001.10012.x11896827
    [Google Scholar]
  61. GazonH. BarbeauB. MesnardJ.M. PeloponeseJ.M.Jr Hijacking of the ap-1 signaling pathway during development of ATL.Front. Microbiol.20188268610.3389/fmicb.2017.0268629379481
    [Google Scholar]
  62. JayakarS.K. LoudigO. Brandwein-GenslerM. Apolipoprotein e promotes invasion in oral squamous cell carcinoma.Am. J. Pathol.2017187102259227210.1016/j.ajpath.2017.06.01628751006
    [Google Scholar]
  63. ChengY. miR-135b-5p targets sirt1 to inhibit deacetylation of c-jun and increase mmp7 expression to promote migration and invasion of nasopharyngeal carcinoma cells.Mol. Biotechnol.202264669370110.1007/s12033‑022‑00457‑535094303
    [Google Scholar]
  64. ChangM.C. ChenC.A. ChenP.J. Mesothelin enhances invasion of ovarian cancer by inducing MMP-7 through MAPK/ERK and JNK pathways.Biochem. J.2012442229330210.1042/BJ2011028221999204
    [Google Scholar]
  65. YuanG. QianL. SongL. Heregulin-β promotes matrix metalloproteinase-7 expression via HER2-mediated AP-1 activation in MCF-7 cells.Mol. Cell. Biochem.20083181-2737910.1007/s11010‑008‑9858‑618600430
    [Google Scholar]
  66. BurgermeisterE. Mitogen-activated protein kinase and exploratory nuclear receptor crosstalk in cancer immunotherapy.Int. J. Mol. Sci.202324191454610.3390/ijms24191454637833991
    [Google Scholar]
  67. NajafiM. AhmadiA. MortezaeeK. Extracellular‐signal‐regulated kinase/mitogen‐activated protein kinase signaling as a target for cancer therapy: an updated review.Cell Biol. Int.201943111206122210.1002/cbin.1118731136035
    [Google Scholar]
  68. YangM. HuangC.Z. Mitogen-activated protein kinase signaling pathway and invasion and metastasis of gastric cancer.World J. Gastroenterol.20152141116731167910.3748/wjg.v21.i41.1167326556994
    [Google Scholar]
  69. PandeyV. BhaskaraV.K. BabuP.P. Implications of mitogen‐activated protein kinase signaling in glioma.J. Neurosci. Res.201694211412710.1002/jnr.2368726509338
    [Google Scholar]
  70. AchkarI.W. AbdulrahmanN. Al-SulaitiH. JosephJ.M. UddinS. MraicheF. Cisplatin based therapy: the role of the mitogen activated protein kinase signaling pathway.J. Transl. Med.20181619610.1186/s12967‑018‑1471‑129642900
    [Google Scholar]
  71. RovidaE. TusaI. Targeting MAPK in cancer 2.0.Int. J. Mol. Sci.20222310570210.3390/ijms2310570235628511
    [Google Scholar]
  72. WangH. WenC. ChenS. ROS/JNK/C-Jun Pathway is involved in chaetocin induced colorectal cancer cells apoptosis and macrophage phagocytosis enhancement.Front. Pharmacol.20211272936710.3389/fphar.2021.72936734776955
    [Google Scholar]
  73. XianL. XiongY. QinL. Jun/Fos promotes migration and invasion of hepatocellular carcinoma cells by enhancing BORIS promoter activity.Int. J. Biochem. Cell Biol.202416910654010.1016/j.biocel.2024.10654038281696
    [Google Scholar]
  74. SannaM.D. GaleottiN. The HDAC1/c-JUN complex is essential in the promotion of nerve injury-induced neuropathic pain through JNK signaling.Eur. J. Pharmacol.20188259910610.1016/j.ejphar.2018.02.03429477655
    [Google Scholar]
  75. VisseR. NagaseH. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry.Circ. Res.200392882783910.1161/01.RES.0000070112.80711.3D12730128
    [Google Scholar]
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