Skip to content
2000
Volume 25, Issue 1
  • ISSN: 1566-5240
  • E-ISSN: 1875-5666

Abstract

Background

We aimed to investigate the relationship between histone deacetylase 2 (HDAC2) and SPARC-related modular calcium binding 2 (SMOC2) and the role of SMOC2 in gallbladder cancer (GBC).

Methods

The expression of HDAC2 and SMOC2 in GBC and normal cells was detected by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), which was also used to detect the mRNA stability of SMOC2. The combination between HDAC2 and SMOC2 was detected by Chromatin immunoprecipitation (ChIP) assay. After silencing and/or overexpressing HDAC2 and SMOC2, cell viability, migration, invasion, and stemness were respectively tested by the Cell Counting Kit-8 (CCK-8), cell scratch, transwell, and sphere-formation assay.

Results

In GBC cells, HDAC2 and SMOC2 were highly expressed. HDAC2 combined with SMOC2 promoted mRNA stability of SMOC2. HDAC2 or SMOC2 overexpression promoted GBC cell metastasis and stemness. SMOC2 overexpression rescued the negative effects of silencing HDAC2 in GBC.

Conclusion

HDAC2 stabilizes SMOC2 to promote metastasis and stemness in gallbladder cancer.

Loading

Article metrics loading...

/content/journals/cmm/10.2174/0115665240257970231013094101
2024-01-03
2025-01-19
Loading full text...

Full text loading...

References

  1. Miranda-FilhoA. PiñerosM. FerreccioC. Gallbladder and extrahepatic bile duct cancers in the Americas: Incidence and mortality patterns and trends.Int. J. Cancer2020147497898910.1002/ijc.32863 31922259
    [Google Scholar]
  2. ValleJ.W. LamarcaA. GoyalL. BarriusoJ. ZhuA.X. New horizons for precision medicine in biliary tract cancers.Cancer Discov.20177994396210.1158/2159‑8290.CD‑17‑0245 28818953
    [Google Scholar]
  3. ZhangP. ZhaiY. CaiY. ZhaoY. LiY. Nanomedicine‐based immunotherapy for the treatment of cancer metastasis.Adv. Mater.20193149190415610.1002/adma.201904156 31566275
    [Google Scholar]
  4. RomanoS. TufanoM. D’ArrigoP. VigoritoV. RussoS. RomanoM.F. Cell stemness, epithelial-to-mesenchymal transition, and immunoevasion: Intertwined aspects in cancer metastasis.Semin. Cancer Biol.20206018119010.1016/j.semcancer.2019.08.015 31422157
    [Google Scholar]
  5. MuñozJ. StangeD.E. SchepersA.G. The Lgr5 intestinal stem cell signature: Robust expression of proposed quiescent ‘+4′ cell markers.EMBO J.201231143079309110.1038/emboj.2012.166 22692129
    [Google Scholar]
  6. RizzinoA. WuebbenE.L. Sox2/Oct4: A delicately balanced partnership in pluripotent stem cells and embryogenesis.Biochim. Biophys. Acta. Gene Regul. Mech.20161859678079110.1016/j.bbagrm.2016.03.006 26992828
    [Google Scholar]
  7. WuT. OuyangG. Matricellular proteins: Multifaceted extracellular regulators in tumor dormancy.Protein Cell20145424925210.1007/s13238‑014‑0023‑6 24563214
    [Google Scholar]
  8. RobertsD.D. Emerging functions of matricellular proteins.Cell. Mol. Life Sci.201168193133313610.1007/s00018‑011‑0779‑2 21833584
    [Google Scholar]
  9. Murphy-UllrichJ.E. SageE.H. Revisiting the matricellular concept.Matrix Biol.20143711410.1016/j.matbio.2014.07.005 25064829
    [Google Scholar]
  10. WongG.S. RustgiA.K. Matricellular proteins: Priming the tumour microenvironment for cancer development and metastasis.Br. J. Cancer2013108475576110.1038/bjc.2012.592 23322204
    [Google Scholar]
  11. LongF. ShiH. LiP. A SMOC2 variant inhibits BMP signaling by competitively binding to BMPR1B and causes growth plate defects.Bone202114211568610.1016/j.bone.2020.115686 33059102
    [Google Scholar]
  12. TakahataY. HaginoH. KimuraA. Smoc1 and Smoc2 regulate bone formation as downstream molecules of Runx2.Commun. Biol.202141119910.1038/s42003‑021‑02717‑7 34667264
    [Google Scholar]
  13. WangY. YangH. SuX. CaoA.A-O. ChenF. ChenP. TGF-β1/SMOC2/AKT and ERK axis regulates proliferation, migration, and fibroblast to myofibroblast transformation in lung fibroblast, contributing with the asthma progression.Hereditas202115847
    [Google Scholar]
  14. GerarduzziC. KumarR.K. TrivediP. Silencing SMOC2 ameliorates kidney fibrosis by inhibiting fibroblast to myofibroblast transformation.JCI Insight201728e9029910.1172/jci.insight.90299 28422762
    [Google Scholar]
  15. JangB.G. KimH.S. BaeJ.M. KimW.H. KimH.U. KangG.H. SMOC2, an intestinal stem cell marker, is an independent prognostic marker associated with better survival in colorectal cancers.Sci. Rep.202010114591
    [Google Scholar]
  16. SuJ.R. KuaiJ.H. LiY.Q. Smoc2 potentiates proliferation of hepatocellular carcinoma cells via promotion of cell cycle progression.World J. Gastroenterol.20162245100531006310.3748/wjg.v22.i45.10053 28018113
    [Google Scholar]
  17. VincentA. OmuraN. HongS.M. JaffeA. EshlemanJ. GogginsM. Genome-wide analysis of promoter methylation associated with gene expression profile in pancreatic adenocarcinoma.Clin. Cancer Res.201117134341435410.1158/1078‑0432.CCR‑10‑3431 21610144
    [Google Scholar]
  18. KimH.S. ChoiJ.H. LeeJ.Y. Downregulation of SMOC2 expression in papillary thyroid carcinoma and its prognostic significance.Sci. Rep.2020101485310.1038/s41598‑020‑61828‑z 32184420
    [Google Scholar]
  19. FuksF. BurgersW.A. BrehmA. Hughes-DaviesL. KouzaridesT. DNA methyltransferase Dnmt1 associates with histone deacetylase activity.Nat. Genet.2000241889110.1038/71750 10615135
    [Google Scholar]
  20. KrämerO.H. HDAC2: A critical factor in health and disease.Trends Pharmacol. Sci.2009301264765510.1016/j.tips.2009.09.007 19892411
    [Google Scholar]
  21. HuX. XingW. ZhaoR. HDAC2 inhibits EMT-mediated cancer metastasis by downregulating the long noncoding RNA H19 in colorectal cancer.J. Exp. Clin. Cancer Res.202039127010.1186/s13046‑020‑01783‑9 33267897
    [Google Scholar]
  22. WangZ. ZhouN. WangW. YuY. XiaL. LiN. HDAC2 interacts with microRNA-503-5p to regulate SGK1 in osteoarthritis.Arthritis Res. Ther.20212317810.1186/s13075‑020‑02373‑y 33750441
    [Google Scholar]
  23. CaiS. ChenW. ZengW. ChengX. LinM. WangJ. Roles of HDAC2, eIF5, and eIF6 in Lung Cancer tumorigenesis.Curr. Med. Sci.202141476476910.1007/s11596‑021‑2389‑z 34403101
    [Google Scholar]
  24. MarcellaL.N. FrancescaP. LuigiM. GianpaoloP. TarikR. AngelaL. HDAC2 depletion promotes osteosarcoma’s stemness both in vitro and in vivo: A study on a putative new target for CSCs directed therapy.J. Exp. Clin. Cancer Res.2018371296
    [Google Scholar]
  25. LivakK.J. SchmittgenT.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)).Method. Methods2013254402208
    [Google Scholar]
  26. ChangC.C. LinB.R. ChenS.T. HsiehT.H. LiY.J. KuoM.Y.P. HDAC2 promotes cell migration/invasion abilities through HIF-1α stabilization in human oral squamous cell carcinoma.J. Oral Pathol. Med.201140756757510.1111/j.1600‑0714.2011.01009.x 21332579
    [Google Scholar]
  27. AhnW.S. KimK.W. BaeS.M. Targeted cellular process profiling approach for uterine leiomyoma using cDNA microarray, proteomics and gene ontology analysis.Int. J. Exp. Pathol.200384626727910.1111/j.0959‑9673.2003.00362.x 14748746
    [Google Scholar]
  28. LeeC.H. KuoW.H. LinC.C. OyangY.J. HuangH.C. MicroRNA-regulated protein-protein interaction networks and their functions in breast cancer.Int. J. Mol. Sci.20131461156011606
    [Google Scholar]
  29. MenendezL. WalkerD. MatyuninaL.V. Identification of candidate methylation-responsive genes in ovarian cancer.Mol. Cancer2007611010.1186/1476‑4598‑6‑10 17254359
    [Google Scholar]
  30. FinnS.P. SmythP. CahillS. Expression microarray analysis of papillary thyroid carcinoma and benign thyroid tissue: emphasis on the follicular variant and potential markers of malignancy.Virchows Arch.2007450324926010.1007/s00428‑006‑0348‑5 17252232
    [Google Scholar]
  31. ShvabA. HaaseG. Ben-ShmuelA. Induction of the intestinal stem cell signature gene SMOC-2 is required for L1-mediated colon cancer progression.Oncogene201635554955710.1038/onc.2015.127 25915847
    [Google Scholar]
  32. BuurmanR. GürlevikE. SchäfferV. Histone deacetylases activate hepatocyte growth factor signaling by repressing microRNA-449 in hepatocellular carcinoma cells.Gastroenterology20121433811820.e1510.1053/j.gastro.2012.05.033 22641068
    [Google Scholar]
  33. WangW. FuL. LiS. XuZ. LiX. Histone deacetylase 11 suppresses p53 expression in pituitary tumor cells.Cell Biol. Int.201741121290129510.1002/cbin.10834 28782861
    [Google Scholar]
  34. KimH.S. PatelK. Muldoon-JacobsK. SIRT3 is a mitochondria-localized tumor suppressor required for maintenance of mitochondrial integrity and metabolism during stress.Cancer Cell2010171415210.1016/j.ccr.2009.11.023 20129246
    [Google Scholar]
  35. SeidelC. SchnekenburgerM. DicatoM. DiederichM. Histone deacetylase 6 in health and disease.Epigenomics20157110311810.2217/epi.14.69 25687470
    [Google Scholar]
  36. ShettyM.G. PaiP. DeaverR.E. SatyamoorthyK. BabithaK.S. Histone deacetylase 2 selective inhibitors: A versatile therapeutic strategy as next generation drug target in cancer therapy.Pharmacol. Res.202117010569510.1016/j.phrs.2021.105695 34082029
    [Google Scholar]
  37. HeJ. ShenS. LuW. HDAC1 promoted migration and invasion binding with TCF12 by promoting EMT progress in gallbladder cancer.Oncotarget2016722327543276410.18632/oncotarget.8740 27092878
    [Google Scholar]
  38. ZhuH. WangC. Retracted: HDAC2 ‐mediated proliferation of trophoblast cells requires the miR‐183/FOXA1/IL‐8 signaling pathway.J. Cell. Physiol.202123642544255810.1002/jcp.30026 33164209
    [Google Scholar]
  39. RuijterA.J.M. GennipA.H. CaronH.N. KempS. KuilenburgA.B.P. Histone deacetylases (HDACs): Characterization of the classical HDAC family.Biochem. J.2003370373774910.1042/bj20021321 12429021
    [Google Scholar]
  40. XuG. ZhuH. ZhangM. XuJ. Histone deacetylase 3 is associated with gastric cancer cell growth via the miR-454-mediated targeting of CHD5.Int. J. Mol. Med.2018411155163 29115379
    [Google Scholar]
  41. BrunetA. SweeneyL.B. SturgillJ.F. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase.Science200430356662011201510.1126/science.1094637 14976264
    [Google Scholar]
  42. HyakusokuH. SanoD. TakahashiH. JunB promotes cell invasion, migration and distant metastasis of head and neck squamous cell carcinoma.J. Exp. Clin. Cancer Res.2016351610.1186/s13046‑016‑0284‑4 26754630
    [Google Scholar]
  43. BradyJ.J. ChuangC.H. GreensideP.G. An Arntl2-driven secretome enables lung adenocarcinoma metastatic self-sufficiency.Cancer Cell201629569771010.1016/j.ccell.2016.03.003 27150038
    [Google Scholar]
/content/journals/cmm/10.2174/0115665240257970231013094101
Loading
/content/journals/cmm/10.2174/0115665240257970231013094101
Loading

Data & Media loading...

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