Abstract
ELK3, an ETS domain-containing transcription factor, participates in various physiological and pathological processes including cell proliferation, migration, angiogenesis, and malignant progression. However, the role of ELK3 in prostate cancer cells and its mechanism are not fully understood. The contribution of ELK3 to prostate cancer progression was investigated in the present study. We showed that silencing of ELK3 by siRNA in prostate cancer cell DU145 induced S-M phase arrest, promoted apoptosis, inhibited cell proliferation and migration in vitro, and suppressed xenograft growth in mice in vivo. In accordance with its ability to arrest cells in S-M phase, the expression of cyclin A and cyclin B was downregulated. In addition, the expression of p53 was upregulated following ELK3 knockdown, while that of antiapoptotic Bcl-2 was decreased. The migration inhibition may partly due to upregulation of SERPINE1 (a serine protease inhibitor) followed ELK3 knockdown. Consistently, downregulation of SERPINE1 resulted in a modest elimination of migration inhibition resulted from ELK3 knockdown. Furthermore, we found that the AKT signaling was activated in ELK3 knockdown cells, and treatment these cells with AKT inhibitor attenuated SERPINE1 expression induced by ELK3 silencing, suggesting that activation of AKT pathway may be one of the reasons for upregulation of SERPINE1 after ELK3 knockdown. In conclusion, modulation of ELK3 expression may control the progression of prostate cancer partly by regulating cell growth, apoptosis, and migration.
Highlights
Prostate cancer (PCa) is the fourth most common cancer type worldwide and the second commonly diagnosed cancer and the fifth leading cause of cancer-related death in males [1]
ELK3 was knocked down in DU145 cells by specific small interfering RNA (siRNA). e protein expression level of ELK3 evaluated by Western blot was significantly reduced in DU145 cells transfected with ELK3-siRNA compared with the one transfected with NC-siRNA. en CCK-8 assay was conducted to determine the effect of ELK3 on cell proliferation. e growth of cells with ELK3 knockdown was significantly inhibited compared with that of controls (Figure 1(a))
Transwell assay results revealed that the migration ability of ELK3-knocked down cells was lower than that of control cells (Figure 1(d)), suggesting that ELK3 may promote migration in DU145 cells. ese results suggested that ELK3 would play a key role in PCa progression
Summary
Prostate cancer (PCa) is the fourth most common cancer type worldwide and the second commonly diagnosed cancer and the fifth leading cause of cancer-related death in males [1]. Recent observations have shown that PCa is an increasingly serious disease among older adolescent and young adult males, possibly due to inadequate diagnosis, and may be caused by obesity, lack of exercise, and environmental carcinogens [5]. The exact molecular mechanism of PCa progress is not yet fully understood. ELK3 ( called Net, SAP-2, or ERP) is an ETS domaincontaining transcription factor that forms a ternary complex transcription factor (TCF) together with ELK-1 and serum response factor accessory protein-1 (SAP-1) and binds to a specific DNA sequence through a purine-rich GGA core sequence to regulate the expression of many genes including proto-oncogenes [6, 7]. ELK3 is a transcriptional repressor, which converts to a transcriptional
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