GCN5 Potentiates Glioma Proliferation and Invasion via STAT3 and AKT Signaling Pathways

Liu, Kun; Zhang, Qing; Lan, Haitao; Wang, Liping; Mou, Pengfei; Shao, Wei; Liu, Dan; Yang, Wensheng; Lin, Zhen; Lin, Qingyuan; Ji, Tao

doi:10.3390/ijms160921897

Cited by 44 publications

(41 citation statements)

References 25 publications

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“…It was demonstrated that GCN5 knockdown is able to significantly repress the TGF-β1-induced elevation of p-STAT3 and p-AKT expression. This indicates that GCN5 can promote the TGF-β1-induced EMT transition, at least partly via the STAT3 and AKT signaling pathways (16). GCN5 and E2F1 may have synergistic effect (23), and the results of the current study also demonstrated that E2F1 is the downstream targeted protein of the STAT3 and AKT pathways; there is an interaction between GCN5 and E2F1 following GCN5 knockdown.…”

Section: Discussionsupporting

confidence: 60%

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Function of GCN5 in the TGF‑β1‑induced epithelial‑to‑mesenchymal transition in breast cancer

Zhao

Pang

2018

Oncol Lett

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Histone acetyltransferase GCN5 is a critical component of the TGF-β/Smad signaling pathway in breast cancer cells; however, it remains unknown whether it is involved in the development and progression of breast cancer. The present study investigated the role of GCN5 in the induction of the EMT by TGF-β1 in breast cancer cells and its underlying molecular mechanism of action. GCN5 activity was elevated and GCN5 mRNA expression and protein expression were increased in MDA-MB231 cells following stimulation with TGF-β1. Furthermore, TGF-β1 stimulation decreased expression of the epithelial cell marker E-cadherin and increased expression of the mesenchymal cell markers, N-cadherin and vimentin, as well as the expression of other EMT markers, including snail and slug. However, these changes were reversed following GCN5 knockdown leading to the downregulation of GCN5 expression. GCN5 knockdown also inhibited the viability, migration and invasion of MDA-MB231 cells, decreased the expression of p-STAT3, p-AKT, MMP9 and E2F1, and increased the expression of p21 in MDA-MB231 cells compared with cells stimulated with TGF-β1 alone. Therefore, GCN5 may work downstream of TGF-β/Smad signaling pathway to regulate the EMT in breast cancer.

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Section: Discussionsupporting

confidence: 60%

“…Histone acetylation serves a vital role in establishing an active chromatin environment for transcriptional regulation (16). Histone lysine acetyltransferases (KATs) help to maintain the balance between histone acetylation and deacetylation (17).…”

Section: Discussionmentioning

confidence: 99%

Function of GCN5 in the TGF‑β1‑induced epithelial‑to‑mesenchymal transition in breast cancer

Zhao

Pang

2018

Oncol Lett

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“…The positive role of GCN5 in the development of various tumors was gradually elucidated, we next questioned whether GCN5 was associated with PFKFB4‐mediated TC cells development (Li, Liu, Zhang, & Ye, ; Liu et al, ; Shao et al, ; Yin et al, ). It is intriguing that GCN5 expression was inhibited by shPFKFB4‐transfected (Figure ).…”

Section: Resultsmentioning

confidence: 99%

“…was associated with PFKFB4-mediated TC cells development (Li, Liu, Zhang, & Ye, 2015;Liu et al, 2015;Shao et al, 2018;Yin et al, 2015). It is intriguing that GCN5 expression was inhibited by shPFKFB4-transfected ( Figure 4).…”

Section: Downregulation Of Pfkfb4 Inhibited Gcn5 Expression and Phomentioning

confidence: 91%

PFKFB4 negatively regulated the expression of histone acetyltransferase GCN5 to mediate the tumorigenesis of thyroid cancer

Chen

You

et al. 2020

Dev Growth Differ

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Thyroid cancer (TC) is the most common malignant endocrine tumor, and its incidence has progressively increased over several decades. Accumulating evidence has suggested that PFKFB4, a critical regulatory enzyme of glycolysis, has been implicated in various solid cancers. However, the exact effect of PFKFB4 on TC remains unclear. Hence, the objective of this work was to investigate the role of PFKFB4 in TC and explore the underlying regulatory mechanisms. Here, we provide evidence that mRNA levels of PFKFB4 were upregulated in TC patients’ thyroids and cell lines. Downregulation of PFKFB4 reduced TC cell viability and inhibited colony formation. In addition, the migration and invasion of TC cells were suppressed by PFKFB4 knockdown, suggesting that PFKFB4 is positively correlated with tumorigenesis of TC. Molecularly, knockdown of PFKFB4 significantly inhibited expression of GCN5 and phosphorylation of PI3K/AKT. Moreover, the suppressive role of shPFKFB4 in TC cell growth was reversed by upregulation of GCN5. Finally, the in vivo experiment indicated that downregulation of PFKF4B suppressed tumor growth in xenografts TC model mice. In total, our results suggested that PFKFB4‐mediated TC tumorigenesis by positively regulating GCN5 and PI3K/AKT signaling. These findings provide new research directions and therapeutic options considering PFKF4B as a novel diagnosis marker and therapeutic target.

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“…GCN5, as a highly conserved histone acetyltransferase, has been reported to play crucial roles in development and etiology of tumors. In several tumors, GCN5 facilitates the expressions of oncogenes (33)(34)(35). Whether abnormal GCN5 is involved in bone diseases remains unknown, however.…”

Section: Discussionmentioning

confidence: 99%

Declining histone acetyltransferase GCN5 represses BMSC‐mediated angiogenesis during osteoporosis

Jing

Liao

et al. 2017

FASEB j.

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Angiogenesis is disrupted in age-related and postmenopausal osteoporosis. However, the mechanisms of the disorder remain elusive. We confirmed in this study that, in accordance with the decrease of H-type vessels, the proangiogenic potential of bone marrow-derived mesenchymal stem cells (BMSCs) declined during osteoporosis. Screening of the histone acetyltransferase family revealed that GCN5 decreased in BMSCs derived from osteoporotic femur. Further analysis identified that GCN5 plays important roles in regulating the proangiogenic potential of BMSCs. GCN5 promoted BMSC-mediated angiogenesis by enhancing H3K9ac levels on the promoter of The decrease of GCN5 in osteoporotic BMSCs led to the decline of proangiogenic capacity. Accordingly, overexpression of GCN5 enhanced the proangiogenic potency of osteoporotic BMSCs. Furthermore, recovering GCN5 expression by lentiviral expression vector significantly attenuated the loss of angiogenesis in ovariectomized mouse femurs. Our study results revealed an epigenetic mechanism controlling BMSC-mediated angiogenesis and provided a novel therapeutic target for osteoporosis treatment.-Jing, H., Liao, L., Su, X., Shuai, Y. Zhang, X., Deng, Z., Jin, Y. Declining histone acetyltransferase GCN5 represses BMSC-mediated angiogenesis during osteoporosis.

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GCN5 Potentiates Glioma Proliferation and Invasion via STAT3 and AKT Signaling Pathways

Cited by 44 publications

References 25 publications

Function of GCN5 in the TGF‑β1‑induced epithelial‑to‑mesenchymal transition in breast cancer

Function of GCN5 in the TGF‑β1‑induced epithelial‑to‑mesenchymal transition in breast cancer

PFKFB4 negatively regulated the expression of histone acetyltransferase GCN5 to mediate the tumorigenesis of thyroid cancer

Declining histone acetyltransferase GCN5 represses BMSC‐mediated angiogenesis during osteoporosis

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