Limits...
The histone demethylase PHF8 promotes prostate cancer cell growth by activating the oncomiR miR-125b.

Ma Q, Chen Z, Jia G, Lu X, Xie X, Jin W - Onco Targets Ther (2015)

Bottom Line: Furthermore, miR-125b is a target of PHF8, and miR-125b seems to be essential for the hyper proliferation of PCa cells in the presence of PHF8.In conclusion, we identify the histone demethylase PHF8 as an oncogenic protein in human PCa.These findings indicate PHF8 as a potential candidate for clinical intervention.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Jinshan Hospital, Fudan University, Shanghai, People's Republic of China.

ABSTRACT

Aims: Prostate cancer (PCa) is the most frequently diagnosed malignancy in men. However, the underlying mechanism is not fully understood. In this study, we aim to research the molecular mechanisms underlying the initiation and progression of PCa.

Results: Plant homeodomain finger protein 8 (PHF8) is upregulated in human PCa tissues and cell lines. PHF8 knockdown attenuates growth and cellular transformation of PCa cells. PHF8 depletion induces PCa cell apoptosis by activating proapoptotic proteins and inactivating antiapoptotic proteins. Furthermore, miR-125b is a target of PHF8, and miR-125b seems to be essential for the hyper proliferation of PCa cells in the presence of PHF8.

Conclusion: In conclusion, we identify the histone demethylase PHF8 as an oncogenic protein in human PCa. These findings indicate PHF8 as a potential candidate for clinical intervention.

No MeSH data available.


Related in: MedlinePlus

PHF8 regulates survival of prostate cancer cells.Notes: (A) Prostate cancer cells were infected with retrovirus carrying sh-Ctrl or sh-PHF8 for 48 hours. Percentage of apoptotic cells was analyzed with FACS. PHF8 knockdown promotes apoptosis (Annexin V-positive) of LNCaP, PC-3, and DU145 cells. **P<0.01. (B) PHF8 knockdown increases percentage of TUNEL-positive cells. Prostate cancer cells were infected with retrovirus carrying sh-Ctrl or sh-PHF8 for 48 hours, and then, TUNEL assay was performed to analyze DNA damage. (C) Representative Western blot showing PHF8 knockdown activates caspase 3, Bax, p21, and PARP and inhibits Bcl-2 in LNCaP cells. LNCaP cells were infected with retrovirus carrying sh-Ctrl or sh-PHF8 for 48 hours, and then, Western blot was performed to analyze protein level.Abbreviations: PHF8, plant homeodomain finger protein 8; FACS, fluorescence-activated cell sorting; TUNEL, transferase-mediated dUTP nick end labeling.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4539089&req=5

f3-ott-8-1979: PHF8 regulates survival of prostate cancer cells.Notes: (A) Prostate cancer cells were infected with retrovirus carrying sh-Ctrl or sh-PHF8 for 48 hours. Percentage of apoptotic cells was analyzed with FACS. PHF8 knockdown promotes apoptosis (Annexin V-positive) of LNCaP, PC-3, and DU145 cells. **P<0.01. (B) PHF8 knockdown increases percentage of TUNEL-positive cells. Prostate cancer cells were infected with retrovirus carrying sh-Ctrl or sh-PHF8 for 48 hours, and then, TUNEL assay was performed to analyze DNA damage. (C) Representative Western blot showing PHF8 knockdown activates caspase 3, Bax, p21, and PARP and inhibits Bcl-2 in LNCaP cells. LNCaP cells were infected with retrovirus carrying sh-Ctrl or sh-PHF8 for 48 hours, and then, Western blot was performed to analyze protein level.Abbreviations: PHF8, plant homeodomain finger protein 8; FACS, fluorescence-activated cell sorting; TUNEL, transferase-mediated dUTP nick end labeling.

Mentions: To investigate whether PHF8 regulates PCa cell proliferation and colony formation by orchestrating survival, we performed fluorescence-activated cell sorting to detect apoptotic cells. We found that PHF8 knockdown significantly increased the number of apoptotic cells in LNCaP, PC-3, and DU145 cells (Figure 3A). We next performed TUNEL assay to investigate whether DNA damage is involved in apoptosis induced by PHF8 knockdown. Markedly, PHF8 knockdown increased the number of TUNEL-positive cells in PCa cells, indicating that PHF8 knockdown induced DNA damage (Figure 3B). Finally, we performed Western blot to analyze the apoptotic signaling pathways. The results indicated that PHF8 knockdown activated apoptotic pathway and inactivated antiapoptotic pathway. In detail, PHF8 knockdown increased the protein level of Bax, p21, cleaved caspase 3, and cleaved PARP, while the antiapoptotic protein Bcl-2 was downregulated when PHF8 was knocked down (Figures 3C and S1). Taken together, PHF8 regulates survival of human PCa cells.


The histone demethylase PHF8 promotes prostate cancer cell growth by activating the oncomiR miR-125b.

Ma Q, Chen Z, Jia G, Lu X, Xie X, Jin W - Onco Targets Ther (2015)

PHF8 regulates survival of prostate cancer cells.Notes: (A) Prostate cancer cells were infected with retrovirus carrying sh-Ctrl or sh-PHF8 for 48 hours. Percentage of apoptotic cells was analyzed with FACS. PHF8 knockdown promotes apoptosis (Annexin V-positive) of LNCaP, PC-3, and DU145 cells. **P<0.01. (B) PHF8 knockdown increases percentage of TUNEL-positive cells. Prostate cancer cells were infected with retrovirus carrying sh-Ctrl or sh-PHF8 for 48 hours, and then, TUNEL assay was performed to analyze DNA damage. (C) Representative Western blot showing PHF8 knockdown activates caspase 3, Bax, p21, and PARP and inhibits Bcl-2 in LNCaP cells. LNCaP cells were infected with retrovirus carrying sh-Ctrl or sh-PHF8 for 48 hours, and then, Western blot was performed to analyze protein level.Abbreviations: PHF8, plant homeodomain finger protein 8; FACS, fluorescence-activated cell sorting; TUNEL, transferase-mediated dUTP nick end labeling.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4539089&req=5

f3-ott-8-1979: PHF8 regulates survival of prostate cancer cells.Notes: (A) Prostate cancer cells were infected with retrovirus carrying sh-Ctrl or sh-PHF8 for 48 hours. Percentage of apoptotic cells was analyzed with FACS. PHF8 knockdown promotes apoptosis (Annexin V-positive) of LNCaP, PC-3, and DU145 cells. **P<0.01. (B) PHF8 knockdown increases percentage of TUNEL-positive cells. Prostate cancer cells were infected with retrovirus carrying sh-Ctrl or sh-PHF8 for 48 hours, and then, TUNEL assay was performed to analyze DNA damage. (C) Representative Western blot showing PHF8 knockdown activates caspase 3, Bax, p21, and PARP and inhibits Bcl-2 in LNCaP cells. LNCaP cells were infected with retrovirus carrying sh-Ctrl or sh-PHF8 for 48 hours, and then, Western blot was performed to analyze protein level.Abbreviations: PHF8, plant homeodomain finger protein 8; FACS, fluorescence-activated cell sorting; TUNEL, transferase-mediated dUTP nick end labeling.
Mentions: To investigate whether PHF8 regulates PCa cell proliferation and colony formation by orchestrating survival, we performed fluorescence-activated cell sorting to detect apoptotic cells. We found that PHF8 knockdown significantly increased the number of apoptotic cells in LNCaP, PC-3, and DU145 cells (Figure 3A). We next performed TUNEL assay to investigate whether DNA damage is involved in apoptosis induced by PHF8 knockdown. Markedly, PHF8 knockdown increased the number of TUNEL-positive cells in PCa cells, indicating that PHF8 knockdown induced DNA damage (Figure 3B). Finally, we performed Western blot to analyze the apoptotic signaling pathways. The results indicated that PHF8 knockdown activated apoptotic pathway and inactivated antiapoptotic pathway. In detail, PHF8 knockdown increased the protein level of Bax, p21, cleaved caspase 3, and cleaved PARP, while the antiapoptotic protein Bcl-2 was downregulated when PHF8 was knocked down (Figures 3C and S1). Taken together, PHF8 regulates survival of human PCa cells.

Bottom Line: Furthermore, miR-125b is a target of PHF8, and miR-125b seems to be essential for the hyper proliferation of PCa cells in the presence of PHF8.In conclusion, we identify the histone demethylase PHF8 as an oncogenic protein in human PCa.These findings indicate PHF8 as a potential candidate for clinical intervention.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Jinshan Hospital, Fudan University, Shanghai, People's Republic of China.

ABSTRACT

Aims: Prostate cancer (PCa) is the most frequently diagnosed malignancy in men. However, the underlying mechanism is not fully understood. In this study, we aim to research the molecular mechanisms underlying the initiation and progression of PCa.

Results: Plant homeodomain finger protein 8 (PHF8) is upregulated in human PCa tissues and cell lines. PHF8 knockdown attenuates growth and cellular transformation of PCa cells. PHF8 depletion induces PCa cell apoptosis by activating proapoptotic proteins and inactivating antiapoptotic proteins. Furthermore, miR-125b is a target of PHF8, and miR-125b seems to be essential for the hyper proliferation of PCa cells in the presence of PHF8.

Conclusion: In conclusion, we identify the histone demethylase PHF8 as an oncogenic protein in human PCa. These findings indicate PHF8 as a potential candidate for clinical intervention.

No MeSH data available.


Related in: MedlinePlus