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Analysis of SET and MYND Domain-Containing Protein 3 (SMYD3) Expression in Gallbladder Cancer: a Pilot Study

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Indian Journal of Surgical Oncology Aims and scope Submit manuscript

Abstract

The Suvar, Enhancer of zeste, and Trithorax (SET) and myeloid-Nervy-DEAF-1 (MYND) domain-containing protein 3 (SMYD3) is a histone lysine methyltransferase and has been recently unveiled to play significant roles in the progression of human cancer via regulating various key cancer-associated genes and pathways. The role of SMYD3 in gallbladder cancer (GBC) still needs to be studied. In the present study, we examined the SMYD3 gene expression at mRNA and protein level to look its impact on risk for developing gallbladder carcinogenesis. SMYD3 expression was evaluated by immunohistochemistry and reverse transcriptase PCR (RT-PCR) from 30 cases each of GBC and cholelithiasis patients. The expression was compared with different clinicopathological parameters. The SMYD3 expression was found to be significantly upregulated in GBC than cholelithiasis group (p < 0.05). The SMYD3 with increased expression level was observed in 73.3% of the GBC cases (p < 0.05). Moreover, mRNA SMYD3 expression was observed in 73.3% of GBC and 10% of control (p < 0.05). Our results indicated that the overexpression of SMYD3 plays an important role in the GBC progression, and SMYD3 may represent useful biomarker for gallbladder cancer patients.

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Data Availability

All data generated or analyzed during this study are included in this published article.

Abbreviations

GBC:

Gallbladder cancer

SMYD3:

Suvar, Enhancer of zeste, and Trithorax (SET) and myeloid-Nervy-DEAF-1 (MYND) domain-containing protein 3

RT-PCR:

Reverse transcriptase polymerase chain reaction

MTC:

Medullary thyroid carcinomas

CC:

Chronic cholecystitis

IHC:

Immunohistochemical

References

  1. Shukla VK, Khandelwal C, Roy SK, Vaidya MP (1985) Primary carcinoma of the gall bladder: a review of a 16-year period at the university hospital. J Surg Oncol 28:32–35

    Article  CAS  PubMed  Google Scholar 

  2. Rakić M, Patrlj L, Kopljar M, Kliček R, Kolovrat M, Loncar B et al (2014) Gallbladder cancer. Hepatobiliary Surg Nutr 3:221–226

    PubMed  PubMed Central  Google Scholar 

  3. Dixit R, Shukla VK, Pandey M (2012) Molecular alterations in gallbladder cancer. World J Pathol 1:31–34

    Google Scholar 

  4. Hundal R, Shaffer EA (2014) Gallbladder cancer: epidemiology and outcome. Clin Epidemiol 6:99–109

    PubMed  PubMed Central  Google Scholar 

  5. Dwivedi AN, Jain S, Dixit R (2015) Gallbladder carcinoma: aggressive malignancy with protean loco-regional and distant spread. World J Clin Cases 3:231–244

    Article  PubMed  PubMed Central  Google Scholar 

  6. Tsai CH, Chen YJ, Yu CJ, Tzeng SR, Wu IC, Kuo WH, Lin MC, Chan NL, Wu KJ, Teng SC (2016) SMYD3-mediated H2A.Z.1 methylation promotes cell cycle and Cancer proliferation. Cancer Res 76:6043–6053

    Article  CAS  PubMed  Google Scholar 

  7. Giakountis A, Moulos P, Sarris ME, Hatzis P, Talianidis I (2017) Smyd3-associated regulatory pathways in cancer. Semin Cancer Biol 42:70–80

    Article  CAS  PubMed  Google Scholar 

  8. Moulos P, Sarris ME, Talianidis I (2016) Mechanism of gene-specificity of oncogenic regulators. Cell Cycle 15:2227–2228

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. He C, Xu J, Zhang J, Xie D, Ye H, Xiao Z, Cai M, Xu K, Zeng Y, Li H, Wang J (2012) High expression of trimethylated histone H3 lysine 4 is associated with poor prognosis in hepatocellular carcinoma. Hum Pathol 43:1425–1435

    Article  CAS  PubMed  Google Scholar 

  10. Huang L, Xu AM (2017) SET and MYND domain containing protein 3 in cancer. Am J Transl Res 9(1):1–14

    PubMed  PubMed Central  Google Scholar 

  11. Luo XG, Zhang CL, Zhao WW, Liu ZP, Liu L, Mu A, Guo S, Wang N, Zhou H, Zhang TC (2014) Histone methyltransferase smyd3 promotes mrtf-a-mediated transactivation of myl9 and migration of mcf-7 breast cancer cells. Cancer Lett 344:129–137

    Article  CAS  PubMed  Google Scholar 

  12. Liu Y, Liu H, Luo X, Deng J, Pan Y, Liang H (2015) Overexpression of SMYD3 and matrix metalloproteinase-9 are associated with poor prognosis of patients with gastric cancer. Tumour Biol 36:4377–4386

    Article  CAS  PubMed  Google Scholar 

  13. Liu Y, Luo X, Deng J, Pan Y, Zhang L, Liang H (2015) Smyd3 overexpression was a risk factor in the biological behavior and prognosis of gastric carcinoma. Tumour Biol 36:2685–2694

    Article  CAS  PubMed  Google Scholar 

  14. Furuta M, Kozaki KI, Tanaka S, Arii S, Imoto I, Inazawa J (2010) Mir-124 and mir-203 are epigenetically silenced tumor-suppressive microRNAs in hepatocellular carcinoma. Carcinogenesis 31:766–776

    Article  CAS  PubMed  Google Scholar 

  15. Zhu Y, Zhu MX, Zhang XD, Xu XE, Wu ZY, Liao LD, Li LY, Xie YM, Wu JY, Zou HY, Xie JJ, Li EM, Xu LY (2016) SMYD3 stimulates EZR and LOXL2 transcription to enhance proliferation, migration, and invasion in esophageal squamous cell carcinoma. Hum Pathol 52:153–163

    Article  CAS  PubMed  Google Scholar 

  16. Hamamoto R, Furukawa Y, Morita M, Iimura Y, Silva FP, Li M, Yagyu R, Nakamura Y (2004) SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells. Nat Cell Biol 6:731–740

    Article  CAS  PubMed  Google Scholar 

  17. Sims RJ, Reinberg D (2004) From chromatin to cancer: a new histone lysine methyltransferase enters the mix. Nat Cell Biol 6:685–687

    Article  CAS  PubMed  Google Scholar 

  18. Hamamoto R, Silva FP, Tsuge M, Nishidate T, Katagiri T, Nakamura Y, Furukawa Y (2006) Enhanced SMYD3 expression is essential for the growth of breast cancer cells. Cancer Sci 97:113–118

    Article  CAS  PubMed  Google Scholar 

  19. Dai B, Wan W, Zhang P, Zhang Y, Pan C, Meng G et al (2015) SET and MYND domain-containing protein 3 is overexpressed in human glioma and contributes to tumorigenicity. Oncol Rep 34(5):2722–2730

    Article  CAS  PubMed  Google Scholar 

  20. Vieira FQ, Costa-Pinheiro P, Almeida-Rios D, Graça I, Monteiro-Reis S, Simões-Sousa S, Carneiro I, Sousa EJ, Godinho MI, Baltazar F, Henrique R, Jerónimo C (2015) Smyd3 contributes to a more aggressive phenotype of prostate cancer and targets cyclin d2 through H4K20me3. Oncotarget 6:13644–13657

    Article  PubMed  PubMed Central  Google Scholar 

  21. Kim JM, Kim K, Schmidt T, Punj V, Tucker H, Rice JC, Ulmer TS, An W (2015) Cooperation between SMYD3 and PC4 drives a distinct transcriptional program in cancer cells. Nucleic Acids Res 43(18):8868–8883

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Peserico A, Germani A, Sanese P, Barbosa AJ, Di Virgilio V, Fittipaldi R et al (2015) A SMYD3 small-molecule inhibitor impairing cancer cell growth. Cell Physiol 230:2447–2460

    Article  CAS  Google Scholar 

  23. Shen B, Tan M, Mu X, Qin Y, Zhang F, Liu Y, Fan Y (2016) Upregulated SMYD3 promotes bladder cancer progression by targeting BCLAF1 and activating autophagy. Tumour Biol 37(6):7371–7381

    Article  CAS  PubMed  Google Scholar 

  24. Van Aller GS, Reynoird N, Barbash O, Huddleston M, Liu S, Zmoos AF et al (2012) Smyd3 regulates cancer cell phenotypes and catalyzes histone H4 lysine 5 methylation. Epigenetics 7(4):340–343

    Article  PubMed  PubMed Central  Google Scholar 

  25. Sponziello M, Durante C, Boichard A, Dima M, Puppin C, Verrienti A, Tamburrano G, di Rocco G, Redler A, Lacroix L, Bidart JM, Schlumberger M, Damante G, Russo D, Filetti S (2014) Epigenetic-related gene expression profile in medullary thyroid cancer revealed the overexpression of the histone methyltransferases EZH2 and SMYD3 in aggressive tumours. Mol Cell Endocrinol 392(1–2):8–13

    Article  CAS  PubMed  Google Scholar 

  26. Zhu CL, Huang Q (2020) Overexpression of the SMYD3 promotes proliferation, migration, and invasion of pancreatic cancer. Dig Dis Sci 65(2):489–499. https://doi.org/10.1007/s10620-019-05797-y

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

Authors would like to acknowledge all the patients who willingly participated in the study.

Funding

Departmental Research Fund.

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Authors and Affiliations

  1. Department of General Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221 005, India

    Pushkar Chandra, Ruhi Dixit, Arvind Pratap & Vijay Kumar Shukla

  2. Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, India

    Suman Mishra & Rajnikant Mishra

Authors
  1. Pushkar Chandra
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  2. Ruhi Dixit
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  3. Arvind Pratap
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  4. Suman Mishra
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  5. Rajnikant Mishra
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  6. Vijay Kumar Shukla
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Contributions

VKS and RM designed and supervised the study. PC and AP collected the data. PC and SM carried out the PCR and IHC experiments. PC and RD analyzed and interpreted the data. RD drafted the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Vijay Kumar Shukla.

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The authors declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee.

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Informed consent was obtained from all individual participants included in the study.

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All the authors have read the manuscript and have mutually agreed for publication of the same in IJSO.

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Chandra, P., Dixit, R., Pratap, A. et al. Analysis of SET and MYND Domain-Containing Protein 3 (SMYD3) Expression in Gallbladder Cancer: a Pilot Study. Indian J Surg Oncol 12 (Suppl 1), 111–117 (2021). https://doi.org/10.1007/s13193-020-01168-6

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  • DOI: https://doi.org/10.1007/s13193-020-01168-6

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