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HDAC9 promotes glioblastoma growth via TAZ-mediated EGFR pathway activation.

Yang R, Wu Y, Wang M, Sun Z, Zou J, Zhang Y, Cui H - Oncotarget (2015)

Bottom Line: Also, HDAC9 interacted with TAZ, a key downstream effector of Hippo pathway.Knockdown of HDAC9 decreased the expression of TAZ.We found that overexpressed TAZ in HDAC9-knockdown cells abrogated the effects induced by HDAC9 silencing both in vitro and in vivo.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400715, P.R. China.

ABSTRACT
Histone deacetylase 9 (HDAC9), a member of class II HDACs, regulates a wide variety of normal and abnormal physiological functions. We found that HDAC9 is over-expressed in prognostically poor glioblastoma patients. Knockdown HDAC9 decreased proliferation in vitro and tumor formation in vivo. HDAC9 accelerated cell cycle in part by potentiating the EGFR signaling pathway. Also, HDAC9 interacted with TAZ, a key downstream effector of Hippo pathway. Knockdown of HDAC9 decreased the expression of TAZ. We found that overexpressed TAZ in HDAC9-knockdown cells abrogated the effects induced by HDAC9 silencing both in vitro and in vivo. We demonstrated that HDAC9 promotes tumor formation of glioblastoma via TAZ-mediated EGFR pathway activation, and provide the evidence for promising target for the treatment of glioblastoma.

No MeSH data available.


Related in: MedlinePlus

Knockdown of HDAC9 induces cell cycle arrest in G1 phase(A) The cell cycle of HDAC9-knockdown U87 cells was analyzed by flow cytometry. (B) The effects of HDAC9 on the cell cycle of U87 cells. (C) The cell cycle of HDAC9-knockdown LN229 cells was analyzed by flow cytometry. (D) The effects of HDAC9 on the cell cycle of LN229 cells. (E, F) Western blot analysis of some cyclins and CDKs expression in HDAC9-knockdown cells; representative blots are shown. (G, H) Quantitative analysis of cyclins and CDKs expression in HDAC9-knockdown cells; GAPDH was used as a loading control; student's t-test was carried out. All data are shown as the mean ± SD, *p < 0.05, **p < 0.01.
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Figure 4: Knockdown of HDAC9 induces cell cycle arrest in G1 phase(A) The cell cycle of HDAC9-knockdown U87 cells was analyzed by flow cytometry. (B) The effects of HDAC9 on the cell cycle of U87 cells. (C) The cell cycle of HDAC9-knockdown LN229 cells was analyzed by flow cytometry. (D) The effects of HDAC9 on the cell cycle of LN229 cells. (E, F) Western blot analysis of some cyclins and CDKs expression in HDAC9-knockdown cells; representative blots are shown. (G, H) Quantitative analysis of cyclins and CDKs expression in HDAC9-knockdown cells; GAPDH was used as a loading control; student's t-test was carried out. All data are shown as the mean ± SD, *p < 0.05, **p < 0.01.

Mentions: Since the cell cycle progression usually regulates cell proliferation, the U87 and LN229 cell cycle was analyzed by flow cytometry to examine whether HDAC9 promotes cell proliferation by accelerating the cell cycle progression. Representative histograms and the results are summarized in Figure 4A, 4B, 4C and 4D, and HDAC9 knockdown resulted in a markedly increase in the percentage of both U87 and LN229 cells in G1 phase. The results demonstrated that knockdown of HDAC9 could induce cell cycle arrest at G1 phase. To confirm the results, we measured the expression of some cyclins and CDKs which could promote cells to pass the G1/S checkpoint. We found that the expression of cyclin E and CDK2 were reduced in the HDAC9-knockdown cells, but no significant changes were found in the expression of cyclin D1, CDK4 and CDK6 (Figure 4E, 4F, 4G and 4H). These results suggested that HDAC9 accelerated cell cycle progression by upregulating of the CCNE-CDK2 complex.


HDAC9 promotes glioblastoma growth via TAZ-mediated EGFR pathway activation.

Yang R, Wu Y, Wang M, Sun Z, Zou J, Zhang Y, Cui H - Oncotarget (2015)

Knockdown of HDAC9 induces cell cycle arrest in G1 phase(A) The cell cycle of HDAC9-knockdown U87 cells was analyzed by flow cytometry. (B) The effects of HDAC9 on the cell cycle of U87 cells. (C) The cell cycle of HDAC9-knockdown LN229 cells was analyzed by flow cytometry. (D) The effects of HDAC9 on the cell cycle of LN229 cells. (E, F) Western blot analysis of some cyclins and CDKs expression in HDAC9-knockdown cells; representative blots are shown. (G, H) Quantitative analysis of cyclins and CDKs expression in HDAC9-knockdown cells; GAPDH was used as a loading control; student's t-test was carried out. All data are shown as the mean ± SD, *p < 0.05, **p < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4480706&req=5

Figure 4: Knockdown of HDAC9 induces cell cycle arrest in G1 phase(A) The cell cycle of HDAC9-knockdown U87 cells was analyzed by flow cytometry. (B) The effects of HDAC9 on the cell cycle of U87 cells. (C) The cell cycle of HDAC9-knockdown LN229 cells was analyzed by flow cytometry. (D) The effects of HDAC9 on the cell cycle of LN229 cells. (E, F) Western blot analysis of some cyclins and CDKs expression in HDAC9-knockdown cells; representative blots are shown. (G, H) Quantitative analysis of cyclins and CDKs expression in HDAC9-knockdown cells; GAPDH was used as a loading control; student's t-test was carried out. All data are shown as the mean ± SD, *p < 0.05, **p < 0.01.
Mentions: Since the cell cycle progression usually regulates cell proliferation, the U87 and LN229 cell cycle was analyzed by flow cytometry to examine whether HDAC9 promotes cell proliferation by accelerating the cell cycle progression. Representative histograms and the results are summarized in Figure 4A, 4B, 4C and 4D, and HDAC9 knockdown resulted in a markedly increase in the percentage of both U87 and LN229 cells in G1 phase. The results demonstrated that knockdown of HDAC9 could induce cell cycle arrest at G1 phase. To confirm the results, we measured the expression of some cyclins and CDKs which could promote cells to pass the G1/S checkpoint. We found that the expression of cyclin E and CDK2 were reduced in the HDAC9-knockdown cells, but no significant changes were found in the expression of cyclin D1, CDK4 and CDK6 (Figure 4E, 4F, 4G and 4H). These results suggested that HDAC9 accelerated cell cycle progression by upregulating of the CCNE-CDK2 complex.

Bottom Line: Also, HDAC9 interacted with TAZ, a key downstream effector of Hippo pathway.Knockdown of HDAC9 decreased the expression of TAZ.We found that overexpressed TAZ in HDAC9-knockdown cells abrogated the effects induced by HDAC9 silencing both in vitro and in vivo.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400715, P.R. China.

ABSTRACT
Histone deacetylase 9 (HDAC9), a member of class II HDACs, regulates a wide variety of normal and abnormal physiological functions. We found that HDAC9 is over-expressed in prognostically poor glioblastoma patients. Knockdown HDAC9 decreased proliferation in vitro and tumor formation in vivo. HDAC9 accelerated cell cycle in part by potentiating the EGFR signaling pathway. Also, HDAC9 interacted with TAZ, a key downstream effector of Hippo pathway. Knockdown of HDAC9 decreased the expression of TAZ. We found that overexpressed TAZ in HDAC9-knockdown cells abrogated the effects induced by HDAC9 silencing both in vitro and in vivo. We demonstrated that HDAC9 promotes tumor formation of glioblastoma via TAZ-mediated EGFR pathway activation, and provide the evidence for promising target for the treatment of glioblastoma.

No MeSH data available.


Related in: MedlinePlus