Tumor Biology

, Volume 37, Issue 6, pp 7371–7381 | Cite as

Upregulated SMYD3 promotes bladder cancer progression by targeting BCLAF1 and activating autophagy

  • Bing Shen
  • Mingyue Tan
  • Xinyu Mu
  • Yan Qin
  • Fang Zhang
  • Yong Liu
  • Yu Fan
Original Article

Abstract

The recent discovery of a large number of histone methyltransferases reveals important roles of these enzymes in regulating tumor development and progression. SMYD3, a histone methyltransferase, is associated with poor prognosis of patients with prostate and gastric cancer. In the study, we attempted to investigate its putative oncogenic role on bladder cancer. Here, we report that SMYD3 frequently amplified in bladder cancer is correlated with bladder cancer progression and poor prognosis. Overexpression of SMYD3 promotes bladder cancer cell proliferation and invasion, whereas SMYD3 knockdown inhibits cancer cell growth and invasion. Mechanically, SMYD3 positively regulates the expression of BCL2-associated transcription factor 1 (BCLAF1). SMYD3 physically interacts with the promoter of BCLAF1 and upregulates its expression by accumulating di- and trimethylation of H3K4 at the BCLAF1 locus. We further show that SMYD3 overexpression in bladder cancer cells promotes autophagy activation, whereas BCLAF1 depletion inhibits SMYD3-induced autophagy. Finally, we demonstrate that SMYD3 promotes bladder cancer progression, at least in part by increasing BCLAF1 expression and activating autophagy. Our results establish a function for SMYD3 in autophagy activation and bladder cancer progression and suggest its candidacy as a new prognostic biomarker and target for clinical management of bladder cancer.

Keywords

SMYD3 BCLAF1 Autophagy Bladder cancer Histone methyltransferases 

Abbreviations

NMIBC

Non-muscle-invasive or superficial bladder cancer

MIBC

Muscle invasive bladder cancer

H3K4

Histone H3 lysine 4

SMYD3

SET and MYND domain containing protein 3

NHU

Normal human urothelial

BCLAF1

BCL2-associated transcription factor 1

Rapa

Rapamycin

Notes

Authors’ Contribution statement

Planned experiments: Y F; Performed experiments: B S, M-y T, X-y M, Y Q, F Z, Y L; Analyzed data: Y F, B S; Contributed reagents or other essential material: F Z, Y L; Wrote the paper: Y F.

Grant support

This work was funded by National Science Foundation of China (Grant No. 81402086).

Conflicts of interest

None

Supplementary material

13277_2015_4410_MOESM1_ESM.docx (109 kb)
ESM 1 (DOCX 108 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Bing Shen
    • 1
  • Mingyue Tan
    • 1
  • Xinyu Mu
    • 1
  • Yan Qin
    • 1
  • Fang Zhang
    • 1
  • Yong Liu
    • 1
  • Yu Fan
    • 1
  1. 1.Department of Renal Transplantation and Urology, Shanghai First People’s HospitalShanghai Jiaotong UniversityShanghaiChina

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