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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

miR-125b knockdown is sufficient to block the effects of PHF8 in prostate cancer cells.Notes: (A) miR-125b knockdown in LNCaP cells. LNCaP cells were transfected with LNA-Ctrl or LNA-antimiR-125b for 48 hours, and then, RNA was harvested and subjected to cDNA synthesis and q-PCR. (B) miR-125b knockdown blocks PHF8 effect on LNCaP cell proliferation. LNCaP cells were transfected with LNA-Ctrl or LNA-antimiR-125b for 24 hours, and then were infected with indicated retrovirus, and the cell number was evaluated with MTT method at 24 hours, 48 hours, and 72 hours postinfection. #P<0.05, ##P<0.01 indicate sh-Ctrl+LNA-Ctrl vs sh-Ctrl+LNA-antimiR-125b; *P<0.05, **P<0.01 indicate sh-Ctrl+LNA-Ctrl vs sh-PHF8+LNA-Ctrl. (C) miR-125b knockdown blocks PHF8 effect on LNCaP cell apoptosis. LNCaP cells were transfected with LNA-Ctrl or LNA-antimiR-125b for 24 hours, and then were infected with the indicated retrovirus for 48 hours, and the percentage of apoptotic cells was analyzed with FACS.Abbreviations: PHF8, plant homeodomain finger protein 8; LNA, locked nucleic acid; ns, no significance; FACS, fluorescence-activated cell sorting.
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f5-ott-8-1979: miR-125b knockdown is sufficient to block the effects of PHF8 in prostate cancer cells.Notes: (A) miR-125b knockdown in LNCaP cells. LNCaP cells were transfected with LNA-Ctrl or LNA-antimiR-125b for 48 hours, and then, RNA was harvested and subjected to cDNA synthesis and q-PCR. (B) miR-125b knockdown blocks PHF8 effect on LNCaP cell proliferation. LNCaP cells were transfected with LNA-Ctrl or LNA-antimiR-125b for 24 hours, and then were infected with indicated retrovirus, and the cell number was evaluated with MTT method at 24 hours, 48 hours, and 72 hours postinfection. #P<0.05, ##P<0.01 indicate sh-Ctrl+LNA-Ctrl vs sh-Ctrl+LNA-antimiR-125b; *P<0.05, **P<0.01 indicate sh-Ctrl+LNA-Ctrl vs sh-PHF8+LNA-Ctrl. (C) miR-125b knockdown blocks PHF8 effect on LNCaP cell apoptosis. LNCaP cells were transfected with LNA-Ctrl or LNA-antimiR-125b for 24 hours, and then were infected with the indicated retrovirus for 48 hours, and the percentage of apoptotic cells was analyzed with FACS.Abbreviations: PHF8, plant homeodomain finger protein 8; LNA, locked nucleic acid; ns, no significance; FACS, fluorescence-activated cell sorting.

Mentions: As we have demonstrated that PHF8 regressed the expression of miR-125b, we wanted to know whether miR-125b is essential for the function of PHF8 in human PCa. We knocked down miR-125b in LNCaP cells using specific LNA-antimiR-125b (Figure 5A). We found that miR-125b knockdown reduced LNCaP cell proliferation and induced apoptosis (Figure 5B and C). However, PHF8 knockdown was unable to affect LNCaP cell proliferation and apoptosis when miR-125b was knocked down (Figure 5B and C). These results demonstrate that miR-125b is critically essential for the function of PHF8 in human PCa.


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)

miR-125b knockdown is sufficient to block the effects of PHF8 in prostate cancer cells.Notes: (A) miR-125b knockdown in LNCaP cells. LNCaP cells were transfected with LNA-Ctrl or LNA-antimiR-125b for 48 hours, and then, RNA was harvested and subjected to cDNA synthesis and q-PCR. (B) miR-125b knockdown blocks PHF8 effect on LNCaP cell proliferation. LNCaP cells were transfected with LNA-Ctrl or LNA-antimiR-125b for 24 hours, and then were infected with indicated retrovirus, and the cell number was evaluated with MTT method at 24 hours, 48 hours, and 72 hours postinfection. #P<0.05, ##P<0.01 indicate sh-Ctrl+LNA-Ctrl vs sh-Ctrl+LNA-antimiR-125b; *P<0.05, **P<0.01 indicate sh-Ctrl+LNA-Ctrl vs sh-PHF8+LNA-Ctrl. (C) miR-125b knockdown blocks PHF8 effect on LNCaP cell apoptosis. LNCaP cells were transfected with LNA-Ctrl or LNA-antimiR-125b for 24 hours, and then were infected with the indicated retrovirus for 48 hours, and the percentage of apoptotic cells was analyzed with FACS.Abbreviations: PHF8, plant homeodomain finger protein 8; LNA, locked nucleic acid; ns, no significance; FACS, fluorescence-activated cell sorting.
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f5-ott-8-1979: miR-125b knockdown is sufficient to block the effects of PHF8 in prostate cancer cells.Notes: (A) miR-125b knockdown in LNCaP cells. LNCaP cells were transfected with LNA-Ctrl or LNA-antimiR-125b for 48 hours, and then, RNA was harvested and subjected to cDNA synthesis and q-PCR. (B) miR-125b knockdown blocks PHF8 effect on LNCaP cell proliferation. LNCaP cells were transfected with LNA-Ctrl or LNA-antimiR-125b for 24 hours, and then were infected with indicated retrovirus, and the cell number was evaluated with MTT method at 24 hours, 48 hours, and 72 hours postinfection. #P<0.05, ##P<0.01 indicate sh-Ctrl+LNA-Ctrl vs sh-Ctrl+LNA-antimiR-125b; *P<0.05, **P<0.01 indicate sh-Ctrl+LNA-Ctrl vs sh-PHF8+LNA-Ctrl. (C) miR-125b knockdown blocks PHF8 effect on LNCaP cell apoptosis. LNCaP cells were transfected with LNA-Ctrl or LNA-antimiR-125b for 24 hours, and then were infected with the indicated retrovirus for 48 hours, and the percentage of apoptotic cells was analyzed with FACS.Abbreviations: PHF8, plant homeodomain finger protein 8; LNA, locked nucleic acid; ns, no significance; FACS, fluorescence-activated cell sorting.
Mentions: As we have demonstrated that PHF8 regressed the expression of miR-125b, we wanted to know whether miR-125b is essential for the function of PHF8 in human PCa. We knocked down miR-125b in LNCaP cells using specific LNA-antimiR-125b (Figure 5A). We found that miR-125b knockdown reduced LNCaP cell proliferation and induced apoptosis (Figure 5B and C). However, PHF8 knockdown was unable to affect LNCaP cell proliferation and apoptosis when miR-125b was knocked down (Figure 5B and C). These results demonstrate that miR-125b is critically essential for the function of PHF8 in human PCa.

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