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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

PHF8 regulates the expression of oncomiR miR-125b.Notes: (A) miR-125b is overexpressed in human PCa tissues. The level of miR-125b in adjacent normal tissues and cancer tissues from PCa patients was analyzed with q-PCR. N=10 in normal group; n=35 in PCa group. (B) miR-125b expression level is correlated with PHF8 expression level. Linear regression analysis was performed to analyze the correlation between miR-125b level and PHF8 mRNA level. N=35. (C) PHF8 knockdown reduces miR-125b expression level. (D) PHF8 promotes miR-125b promoter activity. A pcDNA4.0 vector was used as the control of PHF8 expressing vector, and a pGL3-Basic vector without miR-125b promoter was used as a control luciferase vector.Abbreviations: Ctrl, control; PHF8, plant homeodomain finger protein 8; PCa, prostate cancer.
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f4-ott-8-1979: PHF8 regulates the expression of oncomiR miR-125b.Notes: (A) miR-125b is overexpressed in human PCa tissues. The level of miR-125b in adjacent normal tissues and cancer tissues from PCa patients was analyzed with q-PCR. N=10 in normal group; n=35 in PCa group. (B) miR-125b expression level is correlated with PHF8 expression level. Linear regression analysis was performed to analyze the correlation between miR-125b level and PHF8 mRNA level. N=35. (C) PHF8 knockdown reduces miR-125b expression level. (D) PHF8 promotes miR-125b promoter activity. A pcDNA4.0 vector was used as the control of PHF8 expressing vector, and a pGL3-Basic vector without miR-125b promoter was used as a control luciferase vector.Abbreviations: Ctrl, control; PHF8, plant homeodomain finger protein 8; PCa, prostate cancer.

Mentions: miR-125b is widely accepted as an oncogenic microRNA, and its role has been deeply investigated in human PCa. miR-125b was reported to be an important antiapoptotic factor and regulated drug resistance in human PCa. Our q-PCR results also showed that miR-125b was upregulated in human PCa tissues (Figure 4A), which was consistent with previous reports.13 Furthermore, we performed linear regression analysis to figure out whether miR-125b level is correlated with PHF8 expression in human PCa. The results indicated that miR-125b level was significantly and positively correlated with PHF8 level in human PCa tissues (Figure 4B), indicating that PHF8 may regulate miR-125b. We next knocked down PHF8 in LNCaP cells and found that PHF8 knockdown significantly reduced the level of miR-125b (Figure 4C). Finally, our luciferase assay demonstrated that PHF8 overexpression enhanced the promoter activity of miR-125b (Figure 4D). Taken together, these results demonstrate that PHF8 regulates miR-125b expression 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)

PHF8 regulates the expression of oncomiR miR-125b.Notes: (A) miR-125b is overexpressed in human PCa tissues. The level of miR-125b in adjacent normal tissues and cancer tissues from PCa patients was analyzed with q-PCR. N=10 in normal group; n=35 in PCa group. (B) miR-125b expression level is correlated with PHF8 expression level. Linear regression analysis was performed to analyze the correlation between miR-125b level and PHF8 mRNA level. N=35. (C) PHF8 knockdown reduces miR-125b expression level. (D) PHF8 promotes miR-125b promoter activity. A pcDNA4.0 vector was used as the control of PHF8 expressing vector, and a pGL3-Basic vector without miR-125b promoter was used as a control luciferase vector.Abbreviations: Ctrl, control; PHF8, plant homeodomain finger protein 8; PCa, prostate cancer.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4539089&req=5

f4-ott-8-1979: PHF8 regulates the expression of oncomiR miR-125b.Notes: (A) miR-125b is overexpressed in human PCa tissues. The level of miR-125b in adjacent normal tissues and cancer tissues from PCa patients was analyzed with q-PCR. N=10 in normal group; n=35 in PCa group. (B) miR-125b expression level is correlated with PHF8 expression level. Linear regression analysis was performed to analyze the correlation between miR-125b level and PHF8 mRNA level. N=35. (C) PHF8 knockdown reduces miR-125b expression level. (D) PHF8 promotes miR-125b promoter activity. A pcDNA4.0 vector was used as the control of PHF8 expressing vector, and a pGL3-Basic vector without miR-125b promoter was used as a control luciferase vector.Abbreviations: Ctrl, control; PHF8, plant homeodomain finger protein 8; PCa, prostate cancer.
Mentions: miR-125b is widely accepted as an oncogenic microRNA, and its role has been deeply investigated in human PCa. miR-125b was reported to be an important antiapoptotic factor and regulated drug resistance in human PCa. Our q-PCR results also showed that miR-125b was upregulated in human PCa tissues (Figure 4A), which was consistent with previous reports.13 Furthermore, we performed linear regression analysis to figure out whether miR-125b level is correlated with PHF8 expression in human PCa. The results indicated that miR-125b level was significantly and positively correlated with PHF8 level in human PCa tissues (Figure 4B), indicating that PHF8 may regulate miR-125b. We next knocked down PHF8 in LNCaP cells and found that PHF8 knockdown significantly reduced the level of miR-125b (Figure 4C). Finally, our luciferase assay demonstrated that PHF8 overexpression enhanced the promoter activity of miR-125b (Figure 4D). Taken together, these results demonstrate that PHF8 regulates miR-125b expression 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