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YAP is closely correlated with castration-resistant prostate cancer, and downregulation of YAP reduces proliferation and induces apoptosis of PC-3 cells.

Sheng X, Li WB, Wang DL, Chen KH, Cao JJ, Luo Z, He J, Li MC, Liu WJ, Yu C - Mol Med Rep (2015)

Bottom Line: The frequency of cells that were positive for YAP protein in PCa (78.13%) was significantly higher, compared with para‑PCa (26.67%; P=0.007) and benign prostatic hyperplasia (0%; P=0.002).The proliferative capacity of the transfected group was significantly lower, compared with the negative control group (P=0.022).Therefore, it was concluded that gene transcription and protein expression of YAP may be involved in the development of PCa, particularly CRPC, and may be a novel biomarker for investigation of the occurrence and progression of CRPC.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.

ABSTRACT
Yes-associated protein 65 (YAP65) has been implicated as an oncogene, and its expression is increased in human cancer. Previous studies have demonstrated that alterations in YAP activity may result in tumourigenesis of the prostate. With androgen deprivation therapies becoming progressively ineffective, often leading to life‑threatening androgen‑resistant prostate cancer (CRPC). The present study aimed to analyse the role of YAP in prostate cancer (PCa), particularly in CRPC. YAP protein was detected using immunohistochemistry and western blot analysis in different prostatic tissues. In addition, three specific RNA interference vectors targeting the human YAP gene were synthesised, and PC‑3 cells with a stable inhibition of YAP were obtained by transfection. MTT, flow cytometry, reverse transcription‑quantitative polymerase chain reaction and western blot assays were used to analyse the effects of YAP inhibition on the proliferation and apoptosis of PC‑3 cells. The frequency of cells that were positive for YAP protein in PCa (78.13%) was significantly higher, compared with para‑PCa (26.67%; P=0.007) and benign prostatic hyperplasia (0%; P=0.002). The frequency of cells, which were positive for the expression of YAP exhibited a positive correlation (P=0.008) with the Gleason score, the tumour‑node‑metastasis staging (P=0.033) and the level of prostate specific antigens (P=0.0032) in PCa. The proliferative capacity of the transfected group was significantly lower, compared with the negative control group (P=0.022). The cell‑cycle of the transfected group was arrested in the G1 stage, which was detected using flow cytometry, and there was a significant increase in the apoptosis of cells in the transfected group (P=0.002). The mRNA and protein levels of TEA domain family member 1 were inhibited in the transfected group (P=0.001 and P=0.00, respectively). Therefore, it was concluded that gene transcription and protein expression of YAP may be involved in the development of PCa, particularly CRPC, and may be a novel biomarker for investigation of the occurrence and progression of CRPC. However, the mechanism underlying the modulation of YAP in CRPC remains to be fully elucidated.

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mRNA and protein expression of TEAD1 in the different groups of cells. (A) mRNA expression of TEAD1 was lower in the RNAi-YAP-1 group, determined using reverse transcription-quantitative polymerase chain reaction. (B) Protein expression of TEAD1 was lower in the RNAi-YAP-1 group, determined using western blotting; The mRNA and protein expression levels of TEAD1 were inhibited following YAP knockdown. Data are expressed as the mean ± standard deviation; *P<0.05, **P<0.001 vs. control. RNAi, RNA interference; YAP, yes-associated protein; NT, non-transfected; NC, negative control; TEAD1, TEA domain family member 1; M, marker.
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f8-mmr-12-04-4867: mRNA and protein expression of TEAD1 in the different groups of cells. (A) mRNA expression of TEAD1 was lower in the RNAi-YAP-1 group, determined using reverse transcription-quantitative polymerase chain reaction. (B) Protein expression of TEAD1 was lower in the RNAi-YAP-1 group, determined using western blotting; The mRNA and protein expression levels of TEAD1 were inhibited following YAP knockdown. Data are expressed as the mean ± standard deviation; *P<0.05, **P<0.001 vs. control. RNAi, RNA interference; YAP, yes-associated protein; NT, non-transfected; NC, negative control; TEAD1, TEA domain family member 1; M, marker.

Mentions: TEAD1 is a downstream gene of YAP in the Hippo signalling pathway (5,11). It has been hypothesized that the activity of the TEAD1 gene is regulated by the YAP protein, and binds with the TEAD1 combining domain to form a compound, which generates TEAD1 protein (12). In the present study, the PC-3 cells transfected with RNAi-YAP-1, the mRNA expression was significantly lower, compared with those in the NT and NC groups (P=0.001; Fig. 8A). A western blot assay was also performed, which demonstrated that the protein expression of TEAD1 was also lower in the cells transfected with RNAi-YAP-1 (P=0.005; Fig. 8B). By contrast, YAP was inhibited successfully following TEAD1 inhibition.


YAP is closely correlated with castration-resistant prostate cancer, and downregulation of YAP reduces proliferation and induces apoptosis of PC-3 cells.

Sheng X, Li WB, Wang DL, Chen KH, Cao JJ, Luo Z, He J, Li MC, Liu WJ, Yu C - Mol Med Rep (2015)

mRNA and protein expression of TEAD1 in the different groups of cells. (A) mRNA expression of TEAD1 was lower in the RNAi-YAP-1 group, determined using reverse transcription-quantitative polymerase chain reaction. (B) Protein expression of TEAD1 was lower in the RNAi-YAP-1 group, determined using western blotting; The mRNA and protein expression levels of TEAD1 were inhibited following YAP knockdown. Data are expressed as the mean ± standard deviation; *P<0.05, **P<0.001 vs. control. RNAi, RNA interference; YAP, yes-associated protein; NT, non-transfected; NC, negative control; TEAD1, TEA domain family member 1; M, marker.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581809&req=5

f8-mmr-12-04-4867: mRNA and protein expression of TEAD1 in the different groups of cells. (A) mRNA expression of TEAD1 was lower in the RNAi-YAP-1 group, determined using reverse transcription-quantitative polymerase chain reaction. (B) Protein expression of TEAD1 was lower in the RNAi-YAP-1 group, determined using western blotting; The mRNA and protein expression levels of TEAD1 were inhibited following YAP knockdown. Data are expressed as the mean ± standard deviation; *P<0.05, **P<0.001 vs. control. RNAi, RNA interference; YAP, yes-associated protein; NT, non-transfected; NC, negative control; TEAD1, TEA domain family member 1; M, marker.
Mentions: TEAD1 is a downstream gene of YAP in the Hippo signalling pathway (5,11). It has been hypothesized that the activity of the TEAD1 gene is regulated by the YAP protein, and binds with the TEAD1 combining domain to form a compound, which generates TEAD1 protein (12). In the present study, the PC-3 cells transfected with RNAi-YAP-1, the mRNA expression was significantly lower, compared with those in the NT and NC groups (P=0.001; Fig. 8A). A western blot assay was also performed, which demonstrated that the protein expression of TEAD1 was also lower in the cells transfected with RNAi-YAP-1 (P=0.005; Fig. 8B). By contrast, YAP was inhibited successfully following TEAD1 inhibition.

Bottom Line: The frequency of cells that were positive for YAP protein in PCa (78.13%) was significantly higher, compared with para‑PCa (26.67%; P=0.007) and benign prostatic hyperplasia (0%; P=0.002).The proliferative capacity of the transfected group was significantly lower, compared with the negative control group (P=0.022).Therefore, it was concluded that gene transcription and protein expression of YAP may be involved in the development of PCa, particularly CRPC, and may be a novel biomarker for investigation of the occurrence and progression of CRPC.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.

ABSTRACT
Yes-associated protein 65 (YAP65) has been implicated as an oncogene, and its expression is increased in human cancer. Previous studies have demonstrated that alterations in YAP activity may result in tumourigenesis of the prostate. With androgen deprivation therapies becoming progressively ineffective, often leading to life‑threatening androgen‑resistant prostate cancer (CRPC). The present study aimed to analyse the role of YAP in prostate cancer (PCa), particularly in CRPC. YAP protein was detected using immunohistochemistry and western blot analysis in different prostatic tissues. In addition, three specific RNA interference vectors targeting the human YAP gene were synthesised, and PC‑3 cells with a stable inhibition of YAP were obtained by transfection. MTT, flow cytometry, reverse transcription‑quantitative polymerase chain reaction and western blot assays were used to analyse the effects of YAP inhibition on the proliferation and apoptosis of PC‑3 cells. The frequency of cells that were positive for YAP protein in PCa (78.13%) was significantly higher, compared with para‑PCa (26.67%; P=0.007) and benign prostatic hyperplasia (0%; P=0.002). The frequency of cells, which were positive for the expression of YAP exhibited a positive correlation (P=0.008) with the Gleason score, the tumour‑node‑metastasis staging (P=0.033) and the level of prostate specific antigens (P=0.0032) in PCa. The proliferative capacity of the transfected group was significantly lower, compared with the negative control group (P=0.022). The cell‑cycle of the transfected group was arrested in the G1 stage, which was detected using flow cytometry, and there was a significant increase in the apoptosis of cells in the transfected group (P=0.002). The mRNA and protein levels of TEA domain family member 1 were inhibited in the transfected group (P=0.001 and P=0.00, respectively). Therefore, it was concluded that gene transcription and protein expression of YAP may be involved in the development of PCa, particularly CRPC, and may be a novel biomarker for investigation of the occurrence and progression of CRPC. However, the mechanism underlying the modulation of YAP in CRPC remains to be fully elucidated.

Show MeSH
Related in: MedlinePlus