Skip to content
2000
image of Aspirin Downregulates PDE4D to Inhibit Malignant Progression of Osteosarcoma through the NF-κB/p65 Pathway

Abstract

Introduction

Osteosarcoma is a highly aggressive cancer with a notably low five-year survival rate. Although aspirin has demonstrated potential in inhibiting the malignant progression of osteosarcoma, the underlying mechanisms remain unclear.

Methods

In this study, RNA sequencing (RNA-seq) was employed to identify the downstream targets of aspirin in osteosarcoma cells. Then, we examined the expression and clinical significance of PDE4D using osteosarcoma patient samples, tissue microarrays, and data from the TARGET and GTEx databases. The effects of PDE4D on cell growth and mobility were assessed by CCK-8, colony formation, transwell, and wound-healing assays. To explore how aspirin influenced the NF-κB/p65/PDE4D axis, we performed qRT-PCR, Western blotting, luciferase reporter assays, Additionally, mouse models with subcutaneous tumors were used to confirm the roles of aspirin and PDE4D.

Results

Our results showed that aspirin significantly impeded the proliferation, migration, and invasion of osteosarcoma cells by various functional assays. RNA-seq identified PDE4D as a key target modulated by aspirin treatment in osteosarcoma. Clinically, PDE4D was highly expressed in osteosarcoma cells and tissues, and higher levels of PDE4D were linked to poorer patient outcomes. Functionally, PDE4D served as an oncogene that promoted the malignant traits of osteosarcoma both and . Mechanistically, our findings revealed that NF-κB/p65 directly interacted with the core region of the PDE4D promoter, increasing its expression.

Discussion

The findings of this study reveal a novel mechanism whereby aspirin exerts its anti-tumor effects by inhibiting the NF-κB/p65/PDE4D axis, providing a mechanistic basis for its therapeutic potential. Further validation in different animal models of osteosarcoma is warranted.

Conclusion

Aspirin suppressed the malignant progression of osteosarcoma by targeting the NF-κB/p65/PDE4D axis, positioning PDE4D as a potential therapeutic target for aspirin-based treatment strategies.

© 2026 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cmc/10.2174/0109298673387686251015053130
2026-01-08
2026-02-22

  • From This Site

    /content/journals/cmc/10.2174/0109298673387686251015053130
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Czarnecka A.M. Synoradzki K. Firlej W. Bartnik E. Sobczuk P. Fiedorowicz M. Grieb P. Rutkowski P. Molecular biology of osteosarcoma. Cancers 2020 12 8 2130 10.3390/cancers12082130 32751922
    [Google Scholar]
  2. Kansara M. Teng M.W. Smyth M.J. Thomas D.M. Translational biology of osteosarcoma. Nat Rev Cancer 2014 14 11 722 735 10.1038/nrc3838 25319867
    [Google Scholar]
  3. Sun C. Li S. Ding J. Biomaterials-boosted immunotherapy for osteosarcoma. Adv Healthc Mater 2024 13 23 2400864 10.1002/adhm.202400864 38771618
    [Google Scholar]
  4. Kovac M. Blattmann C. Ribi S. Smida J. Mueller N.S. Engert F. Castro-Giner F. Weischenfeldt J. Kovacova M. Krieg A. Andreou D. Tunn P.U. Dürr H.R. Rechl H. Schaser K.D. Melcher I. Burdach S. Kulozik A. Specht K. Heinimann K. Fulda S. Bielack S. Jundt G. Tomlinson I. Korbel J.O. Nathrath M. Baumhoer D. Exome sequencing of osteosarcoma reveals mutation signatures reminiscent of BRCA deficiency. Nat Commun 2015 6 1 8940 10.1038/ncomms9940 26632267
    [Google Scholar]
  5. Qiu S. Tao L. Zhu Y. Marital status and survival in osteosarcoma patients: An analysis of the surveillance, epidemiology, and end results (SEER) database. Med. Sci. Monit. 2019 25 8190 8203 10.12659/MSM.918048 31672959
    [Google Scholar]
  6. Lu K.H. Lin R.C. Yang J.S. Yang W.E. Reiter R.J. Yang S.F. Molecular and cellular mechanisms of melatonin in osteosarcoma. Cells 2019 8 12 1618 10.3390/cells8121618 31842295
    [Google Scholar]
  7. Luetke A. Meyers P.A. Lewis I. Juergens H. Osteosarcoma treatment – Where do we stand? A state of the art review. Cancer Treat Rev 2014 40 4 523 532 10.1016/j.ctrv.2013.11.006 24345772
    [Google Scholar]
  8. Smrke A. Anderson P.M. Gulia A. Gennatas S. Huang P.H. Jones R.L. Future directions in the treatment of osteosarcoma. Cells 2021 10 1 172 10.3390/cells10010172 33467756
    [Google Scholar]
  9. Whelan J.S. Davis L.E. Osteosarcoma, chondrosarcoma, and chordoma. J. Clin. Oncol 2018 36 2 188 193 10.1200/JCO.2017.75.1743 29220289
    [Google Scholar]
  10. Zheng C. Tang F. Min L. Hornicek F. Duan Z. Tu C. PTEN in osteosarcoma: Recent advances and the therapeutic potential. Biochim. Biophys. Acta. Rev. Cancer 2020 1874 2 188405 10.1016/j.bbcan.2020.188405 32827577
    [Google Scholar]
  11. Liu Y. Li G. Zhang Y. Li L. Zhang Y. Huang X. Wei X. Zhou P. Liu M. zhao G. Feng J. Wang G. Nectin-4 promotes osteosarcoma progression and metastasis through activating PI3K/AKT/NF-κB signaling by down-regulation of miR-520c-3p. Cancer Cell Int. 2022 22 1 252 10.1186/s12935‑022‑02669‑w 35953862
    [Google Scholar]
  12. Prescott L.F. Paracetamol. Am. J. Ther. 2000 7 2 143 148 10.1097/00045391‑200007020‑00011 11319582
    [Google Scholar]
  13. Flossmann E. Rothwell P.M. Effect of aspirin on long-term risk of colorectal cancer: Consistent evidence from randomised and observational studies. Lancet 2007 369 9573 1603 1613 10.1016/S0140‑6736(07)60747‑8 17499602
    [Google Scholar]
  14. Rothwell P.M. Wilson M. Elwin C.E. Norrving B. Algra A. Warlow C.P. Meade T.W. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet 2010 376 9754 1741 1750 10.1016/S0140‑6736(10)61543‑7 20970847
    [Google Scholar]
  15. Algra A.M. Rothwell P.M. Effects of regular aspirin on long-term cancer incidence and metastasis: A systematic comparison of evidence from observational studies versus randomised trials. Lancet Oncol 2012 13 5 518 527 10.1016/S1470‑2045(12)70112‑2 22440112
    [Google Scholar]
  16. Rothwell P.M. Wilson M. Price J.F. Belch J.F.F. Meade T.W. Mehta Z. Effect of daily aspirin on risk of cancer metastasis: A study of incident cancers during randomised controlled trials. Lancet 2012 379 9826 1591 1601 10.1016/S0140‑6736(12)60209‑8 22440947
    [Google Scholar]
  17. Liao D. Zhong L. Duan T. Zhang R.H. Wang X. Wang G. Hu K. Lv X. Kang T. Aspirin suppresses the growth and metastasis of osteosarcoma through the NF-κB pathway. Clin. Cancer Res. 2015 21 23 5349 5359 10.1158/1078‑0432.CCR‑15‑0198 26202947
    [Google Scholar]
  18. Liu H. Xiong C. Liu J. Sun T. Ren Z. Li Y. Geng J. Li X. Aspirin exerts anti-tumor effect through inhibiting Blimp1 and activating ATF4/CHOP pathway in multiple myeloma. Biomed. Pharmacother. 2020 125 110005 10.1016/j.biopha.2020.110005 32070879
    [Google Scholar]
  19. Henry W.S. Laszewski T. Tsang T. Beca F. Beck A.H. McAllister S.S. Toker A. Aspirin suppresses growth in PI3K-mutant breast cancer by activating AMPK and inhibiting mTORC1 signaling. Cancer Res 2017 77 3 790 801 10.1158/0008‑5472.CAN‑16‑2400 27940576
    [Google Scholar]
  20. Ye S. Lee M. Lee D. Ha E.H. Chun E.M. Association of long-term use of low-dose aspirin as chemoprevention with risk of lung cancer. JAMA Netw Open 2019 2 3 e190185 10.1001/jamanetworkopen.2019.0185 30821825
    [Google Scholar]
  21. Wang Y. Zhao L. Geng Y. Yuan H. Hou C. Zhang H. Yang G. Zhang X. Aspirin modulates succinylation of PGAM1K99 to restrict the glycolysis through NF-κB/HAT1/PGAM1 signaling in liver cancer. Acta Pharmacol Sin 2023 44 1 211 220 10.1038/s41401‑022‑00945‑z 35835856
    [Google Scholar]
  22. Wu L. Luo Z. Liu Y. Jia L. Jiang Y. Du J. Guo L. Bai Y. Liu Y. Aspirin inhibits RANKL-induced osteoclast differentiation in dendritic cells by suppressing NF-κB and NFATc1 activation. Stem. Cell. Res. Ther. 2019 10 1 375 10.1186/s13287‑019‑1500‑x 31805984
    [Google Scholar]
  23. Jiang W. Yan Y. Chen M. Luo G. Hao J. Pan J. Hu S. Guo P. Li W. Wang R. Zuo Y. Sun Y. Sui S. Yu W. Pan Z. Zou K. Zheng Z. Deng W. Wu X. Guo W. Aspirin enhances the sensitivity of colon cancer cells to cisplatin by abrogating the binding of NF-κB to the COX-2 promoter. Aging (Albany NY) 2020 12 1 611 627 10.18632/aging.102644 31905343
    [Google Scholar]
  24. Khan P. Bhattacharya A. Sengupta D. Banerjee S. Adhikary A. Das T. Aspirin enhances cisplatin sensitivity of resistant non-small cell lung carcinoma stem-like cells by targeting mTOR-Akt axis to repress migration. Sci. Rep. 2019 9 1 16913 10.1038/s41598‑019‑53134‑0 31729456
    [Google Scholar]
  25. Khan F.U. Owusu-Tieku N.Y.G. Dai X. Liu K. Wu Y. Tsai H.I. Chen H. Sun C. Huang L. Wnt/β-catenin pathway-regulated fibromodulin expression is crucial for breast cancer metastasis and inhibited by Aspirin. Front Pharmacol 2019 10 1308 10.3389/fphar.2019.01308 31824307
    [Google Scholar]
  26. Conti M. Beavo J. Biochemistry and physiology of cyclic nucleotide phosphodiesterases: Essential components in cyclic nucleotide signaling. Annu. Rev. Biochem 2007 76 1 481 511 10.1146/annurev.biochem.76.060305.150444 17376027
    [Google Scholar]
  27. Pullamsetti S.S. Banat G.A. Schmall A. Szibor M. Pomagruk D. Hänze J. Kolosionek E. Wilhelm J. Braun T. Grimminger F. Seeger W. Schermuly R.T. Savai R. Phosphodiesterase-4 promotes proliferation and angiogenesis of lung cancer by crosstalk with HIF. Oncogene 2013 32 9 1121 1134 10.1038/onc.2012.136 22525277
    [Google Scholar]
  28. Sarwar M. Sandberg S. Abrahamsson P.A. Persson J.L. Protein kinase A (PKA) pathway is functionally linked to androgen receptor (AR) in the progression of prostate cancer. Urol. Oncol 2014 32 1 25.e1-12 10.1016/j.urolonc.2012.08.019.
    [Google Scholar]
  29. Goldhoff P. Warrington N.M. Limbrick D.D. Hope A. Woerner B.M. Jackson E. Perry A. Piwnica-Worms D. Rubin J.B. Targeted inhibition of cyclic AMP phosphodiesterase-4 promotes brain tumor regression. Clin. Cancer Res. 2008 14 23 7717 7725 10.1158/1078‑0432.CCR‑08‑0827 19047098
    [Google Scholar]
  30. Narita M. Murata T. Shimizu K. Nakagawa T. Sugiyama T. Inui M. Hiramoto K. Tagawa T. A role for cyclic nucleotide phosphodiesterase 4 in regulation of the growth of human malignant melanoma cells. Oncol. Rep. 2007 17 5 1133 1139 10.3892/or.17.5.1133 17390056
    [Google Scholar]
  31. Murata K. Sudo T. Kameyama M. Fukuoka H. Mukai M. Doki Y. Sasaki Y. Ishikawa O. Kimura Y. Imaoka S. Cyclic AMP specific phosphodiesterase activity and colon cancer cell motility. Clin. Exp. Metastasis 2000 18 7 599 604 10.1023/A:1011926116777 11688965
    [Google Scholar]
  32. Jeong M.H. Urquhart G. Lewis C. Chi Z. Jewell J.L. Inhibition of phosphodiesterase 4D suppresses mTORC1 signaling and pancreatic cancer growth. JCI Insight 2023 8 13 e158098 10.1172/jci.insight.158098 37427586
    [Google Scholar]
  33. Cao M. Nawalaniec K. Ajay A.K. Luo Y. Moench R. Jin Y. Xiao S. Hsiao L.L. Waaga-Gasser A.M. PDE4D targeting enhances anti-tumor effects of sorafenib in clear cell renal cell carcinoma and attenuates MAPK/ERK signaling in a CRAF-dependent manner. Transl. Oncol. 2022 19 101377 10.1016/j.tranon.2022.101377 35196602
    [Google Scholar]
  34. Chen L. Gao H. Liang J. Qiao J. Duan J. Shi H. Zhen T. Li H. Zhang F. Zhu Z. Han A. miR-203a-3p promotes colorectal cancer proliferation and migration by targeting PDE4D. Am. J. Cancer Res. 2018 8 12 2387 2401 30662799
    [Google Scholar]
  35. Zhao M. Bu Y. Feng J. Zhang H. Chen Y. Yang G. Liu Z. Yuan H. Yuan Y. Liu L. Yun H. Wang J. Zhang X. SPIN1 triggers abnormal lipid metabolism and enhances tumor growth in liver cancer. Cancer Lett 2020 470 54 63 10.1016/j.canlet.2019.11.032 31790762
    [Google Scholar]
  36. Arar N.M. Pati P. Kashyap A. Khartchenko A.F. Goksel O. Kaigala G.V. Gabrani M. High-quality immunohistochemical stains through computational assay parameter optimization. IEEE Trans. Biomed. Eng. 2019 66 10 2952 2963 10.1109/TBME.2019.2899156 30762525
    [Google Scholar]
  37. Hinton K. Kirk A. Paul P. Persad S. Regulation of the epithelial to mesenchymal transition in osteosarcoma. Biomolecules 2023 13 2 398 10.3390/biom13020398 36830767
    [Google Scholar]
  38. Wang Y. Feng J. Zhao L. Zhao M. Wei X. Geng Y. Yuan H. Hou C. Zhang H. Wang G. Yang G. Zhang X. Aspirin triggers ferroptosis in hepatocellular carcinoma cells through restricting NF-κB p65-activated SLC7A11 transcription. Acta. Pharmacol. Sin. 2023 44 8 1712 1724 10.1038/s41401‑023‑01062‑1 36829052
    [Google Scholar]
  39. Hua H. Zhang H. Kong Q. Wang J. Jiang Y. Complex roles of the old drug aspirin in cancer chemoprevention and therapy. Med. Res. Rev. 2019 39 1 114 145 10.1002/med.21514 29855050
    [Google Scholar]
  40. Xu X.R. Yousef G.M. Ni H. Cancer and platelet crosstalk: Opportunities and challenges for aspirin and other antiplatelet agents. Blood 2018 131 16 1777 1789 10.1182/blood‑2017‑05‑743187 29519806
    [Google Scholar]
  41. Ying J. Zhou H. Liu P. You Q. Kuang F. Shen Y. Hu Z. Aspirin inhibited the metastasis of colon cancer cells by inhibiting the expression of toll-like receptor 4. Cell Biosci. 2018 8 1 1 10.1186/s13578‑017‑0198‑7 29308184
    [Google Scholar]
  42. Ricciotti E. Wangensteen K.J. FitzGerald G.A. Aspirin in hepatocellular carcinoma. Cancer Res. 2021 81 14 3751 3761 10.1158/0008‑5472.CAN‑21‑0758 33893087
    [Google Scholar]
  43. Guo C.G. Ma W. Drew D.A. Cao Y. Nguyen L.H. Joshi A.D. Ng K. Ogino S. Meyerhardt J.A. Song M. Leung W.K. Giovannucci E.L. Chan A.T. Aspirin use and risk of colorectal cancer among older adults. JAMA Oncol. 2021 7 3 428 435 10.1001/jamaoncol.2020.7338 33475710
    [Google Scholar]
  44. Garg P. Ramisetty S. Nair M. Kulkarni P. Horne D. Salgia R. Singhal S.S. Strategic advancements in targeting the PI3K/AKT/mTOR pathway for Breast cancer therapy. Biochem. Pharmacol. 2025 236 116850 10.1016/j.bcp.2025.116850 40049296
    [Google Scholar]
  45. Glaviano A. Foo A.S.C. Lam H.Y. Yap K.C.H. Jacot W. Jones R.H. Eng H. Nair M.G. Makvandi P. Geoerger B. Kulke M.H. Baird R.D. Prabhu J.S. Carbone D. Pecoraro C. Teh D.B.L. Sethi G. Cavalieri V. Lin K.H. Javidi-Sharifi N.R. Toska E. Davids M.S. Brown J.R. Diana P. Stebbing J. Fruman D.A. Kumar A.P. PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer. Mol. Cancer 2023 22 1 138 10.1186/s12943‑023‑01827‑6 37596643
    [Google Scholar]
  46. Chen Z. Wang C. Dong H. Wang X. Gao F. Zhang S. Zhang X. Aspirin has a better effect on PIK3CA mutant colorectal cancer cells by PI3K/Akt/Raptor pathway. Mol. Med. 2020 26 1 14 10.1186/s10020‑020‑0139‑5 32000660
    [Google Scholar]
  47. Ren G. Ma Y. Wang X. Zheng Z. Li G. Aspirin blocks AMPK/SIRT3-mediated glycolysis to inhibit NSCLC cell proliferation. Eur. J. Pharmacol. 2022 932 175208 10.1016/j.ejphar.2022.175208 35981603
    [Google Scholar]
  48. Xu E. Hu M. Liu Y. Aspirin inhibits proliferation and metastasis of canine mammary gland tumor cells through Wnt signaling axis. Transl. Cancer Res. 2021 10 2 589 601 10.21037/tcr‑20‑3172 35116393
    [Google Scholar]
  49. Deng L. Hu S. Baydoun A.R. Chen J. Chen X. Cong X. Aspirin induces apoptosis in mesenchymal stem cells requiring Wnt/β catenin pathway. Cell Prolif 2009 42 6 721 730 10.1111/j.1365‑2184.2009.00639.x 19706045
    [Google Scholar]
  50. Nath N. Vassell R. Chattopadhyay M. Kogan M. Kashfi K. Nitro-aspirin inhibits MCF-7 breast cancer cell growth: Effects on COX-2 expression and Wnt/β-catenin/TCF-4 signaling. Biochem. Pharmacol. 2009 78 10 1298 1304 10.1016/j.bcp.2009.06.104 19576865
    [Google Scholar]
  51. Bos C.L. Kodach L.L. van den Brink G.R. Diks S.H. van Santen M.M. Richel D.J. Peppelenbosch M.P. Hardwick J.C.H. Effect of aspirin on the Wnt/β-catenin pathway is mediated via protein phosphatase 2A. Oncogene 2006 25 49 6447 6456 10.1038/sj.onc.1209658 16878161
    [Google Scholar]
  52. Dai T. Xue X. Huang J. Yang Z. Xu P. Wang M. Xu W. Feng Z. Zhu W. Xu Y. Chen J. Li S. Meng Q. SCP2 mediates the transport of lipid hydroperoxides to mitochondria in chondrocyte ferroptosis. Cell Death Discov. 2023 9 1 234 10.1038/s41420‑023‑01522‑x 37422468
    [Google Scholar]
  53. Shi T. Gong J. Fujita K. Nishiyama N. Iwama H. Liu S. Nakahara M. Yoneyama H. Morishita A. Nonura T. Kobara H. Okano K. Suzuki Y. Masaki T. Aspirin inhibits cholangiocarcinoma cell proliferation via cell cycle arrest in vitro and in vivo. Int. J. Oncol. 2020 58 2 199 210 10.3892/ijo.2020.5165 33491760
    [Google Scholar]
  54. Liu Y. Feng J. Sun M. Liu B. Yang G. Bu Y. Zhao M. Wang T. Zhang W. Yuan H. Zhang X. Aspirin inhibits the proliferation of hepatoma cells through controlling GLUT1-mediated glucose metabolism. Acta. Pharmacol. Sin. 2019 40 1 122 132 10.1038/s41401‑018‑0014‑x 29925918
    [Google Scholar]
  55. Tang Q.L. Xie X.B. Wang J. Chen Q. Han A.J. Zou C.Y. Yin J.Q. Liu D.W. Liang Y. Zhao Z.Q. Yong B.C. Zhang R.H. Feng Q.S. Deng W.G. Zhu X.F. Zhou B.P. Zeng Y.X. Shen J.N. Kang T. Glycogen synthase kinase-3β, NF-κB signaling, and tumorigenesis of human osteosarcoma. J. Natl. Cancer Inst. 2012 104 10 749 763 10.1093/jnci/djs210 22534782
    [Google Scholar]
  56. Rahrmann E.P. Collier L.S. Knutson T.P. Doyal M.E. Kuslak S.L. Green L.E. Malinowski R.L. Roethe L. Akagi K. Waknitz M. Huang W. Largaespada D.A. Marker P.C. Identification of PDE4D as a proliferation promoting factor in prostate cancer using a Sleeping Beauty transposon-based somatic mutagenesis screen. Cancer Res. 2009 69 10 4388 4397 10.1158/0008‑5472.CAN‑08‑3901 19401450
    [Google Scholar]
  57. Xu T. Wu S. Yuan Y. Yan G. Xiao D. Knockdown of phosphodiesterase 4D inhibits nasopharyngeal carcinoma proliferation via the epidermal growth factor receptor signaling pathway. Oncol. Lett. 2014 8 5 2110 2116 10.3892/ol.2014.2422 25289091
    [Google Scholar]
  58. Liu F. Ma J. Wang K. Li Z. Jiang Q. Chen H. Li W. Xia J. High expression of PDE4D correlates with poor prognosis and clinical progression in pancreaticductal adenocarcinoma. J. Cancer 2019 10 25 6252 6260 10.7150/jca.35443 31772658
    [Google Scholar]
  59. Ge X. Milenkovic L. Suyama K. Hartl T. Purzner T. Winans A. Meyer T. Scott M.P. Phosphodiesterase 4D acts downstream of Neuropilin to control Hedgehog signal transduction and the growth of medulloblastoma. eLife 2015 4 e07068 10.7554/eLife.07068 26371509
    [Google Scholar]
  60. Ren H. Chen Y. Ao Z. Cheng Q. Yang X. Tao H. Zhao L. Shen A. Li P. Fu Q. PDE4D binds and interacts with YAP to cooperatively promote HCC progression. Cancer Lett. 2022 541 215749 10.1016/j.canlet.2022.215749 35597479
    [Google Scholar]
  61. Lusardi M. Rapetti F. Spallarossa A. Brullo C. PDE4D: A multipurpose pharmacological target. Int. J. Mol. Sci. 2024 25 15 8052 10.3390/ijms25158052 39125619
    [Google Scholar]
  62. Kolosionek E. Savai R. Ghofrani H.A. Weissmann N. Guenther A. Grimminger F. Seeger W. Banat G.A. Schermuly R.T. Pullamsetti S.S. Expression and activity of phosphodiesterase isoforms during epithelial mesenchymal transition: The role of phosphodiesterase 4. Mol. Biol. Cell. 2022 33 9 cor2 10.1091/mbc.E09‑01‑0019_corr 35862500
    [Google Scholar]
  63. Lin D.C. Xu L. Ding L.W. Sharma A. Liu L.Z. Yang H. Tan P. Vadgama J. Karlan B.Y. Lester J. Urban N. Schummer M. Doan N. Said J.W. Sun H. Walsh M. Thomas C.J. Patel P. Yin D. Chan D. Koeffler H.P. Genomic and functional characterizations of phosphodiesterase subtype 4D in human cancers. Proc. Natl. Acad. Sci. USA 2013 110 15 6109 6114 10.1073/pnas.1218206110 23536305
    [Google Scholar]
  64. Delyon J. Servy A. Laugier F. André J. Ortonne N. Battistella M. Mourah S. Bensussan A. Lebbé C. Dumaz N. PDE4D promotes FAK-mediated cell invasion in BRAF-mutated melanoma. Oncogene 2017 36 23 3252 3262 10.1038/onc.2016.469 28092671
    [Google Scholar]
  65. Deng Y. Sun S. Runx1 promotes neuronal injury in ischemic stroke through mediating miR-203-3p/Pde4d axis. Brain Inj. 2024 38 12 1035 1045 10.1080/02699052.2024.2373914 38994671
    [Google Scholar]
  66. Hu W. Jiang Y. Wen C. Zeng Y. Jia M. MiR-149-5p inhibits cell proliferation, promotes cell apoptosis and retards cell cycle of IL-22-stimulated HaCaT and NHEK keratinocytes via regulating PDE4D. Cytokine 2023 164 156123 10.1016/j.cyto.2023.156123 36796259
    [Google Scholar]
  67. Huang Y. Zheng Y. Wang Q. Qi C. Rolipram suppresses migration and invasion of human choriocarcinoma cells by inhibiting phosphodiesterase 4-mediated epithelial-mesenchymal transition. J. Biochem. Mol. Toxicol. 2023 37 7 e23363 10.1002/jbt.23363 37020384
    [Google Scholar]
  68. Qiang Z. Zhou Z. Peng T. Jiang P. Shi N. Njoya E.M. Azimova B. Liu W. Chen W. Zhang G. Wang F. Inhibition of TPL2 by interferon-α suppresses bladder cancer through activation of PDE4D. J. Exp. Clin. Cancer Res. 2018 37 1 288 10.1186/s13046‑018‑0971‑4 30482227
    [Google Scholar]
  69. Wang T. Fu X. Jin T. Zhang L. Liu B. Wu Y. Xu F. Wang X. Ye K. Zhang W. Ye L. Aspirin targets P4HA2 through inhibiting NF-κB and LMCD1-AS1/let-7g to inhibit tumour growth and collagen deposition in hepatocellular carcinoma. EBioMedicine 2019 45 168 180 10.1016/j.ebiom.2019.06.048 31278071
    [Google Scholar]
  70. Yuan Y. Yuan H. Geng Y. Zhao L. Yun H. Wang Y. Yang G. Zhang X. Aspirin modulates 2-hydroxyisobutyrylation of ENO1K281 to attenuate the glycolysis and proliferation of hepatoma cells. Biochem. Biophys. Res. Commun. 2021 560 172 178 10.1016/j.bbrc.2021.04.083 34000466
    [Google Scholar]
  71. Giridharan S. Srinivasan M. Mechanisms of NF-κB p65 and strategies for therapeutic manipulation. J. Inflamm. Res. 2018 11 407 419 10.2147/JIR.S140188 30464573
    [Google Scholar]
  72. Zhang D. Zhang J.W. Xu H. Chen X. Gao Y. Jiang H.G. Wang Y. Wu H. Yang L. Wang W.B. Dai J. Xia L. Peng J. Zhou F.X. Therapy-induced senescent tumor cell-derived extracellular vesicles promote colorectal cancer progression through SERPINE1-mediated NF-κB p65 nuclear translocation. Mol. Cancer 2024 23 1 70 10.1186/s12943‑024‑01985‑1 38576002
    [Google Scholar]
  73. Chen S. Zhang D. Du Y. Shi J. Gu S. Zhou X. Yu H. Wang F. Chen J. Cui H. Targeting TRAF6/IRF3 axis to inhibit NF-κB-p65 nuclear translocation enhances the chemosensitivity of 5-FU and reverses the proliferation of gastric cancer. Cell Death Dis. 2024 15 12 924 10.1038/s41419‑024‑07290‑5 39706834
    [Google Scholar]
/content/journals/cmc/10.2174/0109298673387686251015053130
Loading
Aspirin Downregulates PDE4D to Inhibit Malignant Progression of Osteosarcoma through the NF-κB/p65 Pathway
Bentham Science Publishers ; https://doi.org/10.2174/0109298673387686251015053130
/content/journals/cmc/10.2174/0109298673387686251015053130
/content/journals/cmc/10.2174/0109298673387686251015053130
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
Keywords: NF-κB/p65 ; osteosarcoma ; PDE4D ; Aspirin ; cancer cells ; malignant progression

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