BZW1 promotes cell proliferation in prostate cancer by regulating TGF-β1/Smad pathway

Cell Cycle. 2021 May;20(9):894-902. doi: 10.1080/15384101.2021.1909242. Epub 2021 Apr 22.

Abstract

Recently, basic leucine zipper and the W2 domain-containing protein 1 (BZW1) are reported to be implicated in tumor progression. However, the role of BZW1 in prostate cancer remains unknown. This study is aimed to investigate the expression of BZW1 and its influence on cell proliferation in prostate cancer. Then, the expression levels of BZW1 were measured in 136 cases of prostate cancer and matched adjacent non-cancerous prostate tissues by quantificational real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The effect of BZW1 on cell proliferation was further explored. QRT-PCR analysis showed that the mRNA levels of BZW1 in prostate cancer were significantly greater compared with those in matched adjacent non-cancerous prostate tissues (P< 0.001). IHC results showed that the high-expression rates of BZW1 in prostate cancer and matched adjacent non-cancerous prostate tissues were 68.4% and 32.4%, and the difference was statistically significant (P< 0.001). BZW1 high expression significantly correlated with T stage, lymph node metastasis, prostate-specific antigen (PSA) and Gleason score (P< 0.05). Patients with BZW1 high expression presented unfavorable prognosis compared with those with BZW1 low expression (P= 0.002). In addition, CCK-8 and colony formation assays revealed that BZW1 overexpression significantly promoted cell proliferation in vitro. Tumor xenograft has shown that BZW1 knockdown significantly inhibited tumor growth in vivo. Moreover, BZW1 overexpression activated the TGF-β1/Smad1/Smad3 pathway. Therefore, these data indicate that BZW1 overexpression predicts poorer prognosis and promotes cell proliferation in prostate cancer by regulating TGF-β1/Smad pathway.

Keywords: BZW1; biomarker; prognosis; prostate cancer; survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology*
  • Signal Transduction*
  • Smad Proteins / metabolism*
  • Transforming Growth Factor beta1 / metabolism*

Substances

  • BZW1 protein, human
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Smad Proteins
  • Transforming Growth Factor beta1

Grants and funding

This work was supported by the Xinjiang Tianshan Innovation Team Foundation Funded Project (No. 2020D14029).