Histone deacetylase�5 promotes the proliferation and invasion of lung cancer cells

Abstract

Histone deacetylase 5 (HDAC5), as a member of the class IIa family of HDACs, is frequently dysregulated in human malignancies. However, little is known regarding the specific role of HDAC5 in lung cancer. We aimed to evaluate HDAC5 expression in human lung cancer and to determine the effects of HDAC5 on lung cancer cells. First, the expression levels of both HDAC5 protein and mRNA were evaluated in lung cancer tissues and cell lines by western blot analysis and RT‑qPCR, and the results suggested that HDAC5 was significantly upregulated in human lung cancer tissues and cell lines. To address the effects of HDAC5 on the biological behavior of human lung adenocarcinoma cells, we generated human lung cancer A549 cell lines in which HDAC5 was either overexpressed or depleted. The results indicated that overexpression of HDAC5 significantly promoted the proliferation and invasion, and inhibited the apoptosis of A549 cells. On the contrary, HDAC5 knockdown largely decreased the proliferation and invasion and enhanced the apoptosis of A549 cells. Furthermore, we demonstrated that HDAC5 overexpression promoted the expression of DLL4, Six1, Notch 1 and Twist 1 in A549 cells. Downregulation of HDAC5 caused a significant inhibition of the expression of DLL4, Six1, Notch 1 and Twist 1 in A549 cells. Taken together, our data demonstrated that HDAC5 displayed a significant upregulation in lung cancer, and elevated HDAC5 might be involved in the potentiation of proliferation and invasion of lung cancer cells, as well as the inhibition of lung cancer cell apoptosis by the upregulation of DLL4, Six1, Notch 1 and Twist 1. The present study may provide an evidence for the potential application of HDAC5 inhibitors in the therapy of lung cancer.

GZ17-6.02 Interacts With [MEK1/2 and B-RAF Inhibitors] to Kill Melanoma Cells

“…HDAC5 is a class II HDAC, can associate with HDAC3 and HDAC4, and acts to repress transcription, for example the transporter GLUT4 (25,26). Over-expression of HDAC5 in melanoma, and in other malignancies, is associated with enhanced growth and a shorter patient survival (27,28). HDAC6 is cytosolic and regulates acetylation of HSP90 and tubulin, thus impacting signaling by proteins that are chaperoned by HSP90, e.g.…”

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“…HDAC5 protein is expressed in lung, brain, myocardium, skeletal muscle, and placenta, and accumulating evidence indicates that it has variable expression and functions in different types of tumor: HDAC5 is overexpressed in breast cancer ( 19 , 20 ), hepatocellular carcinoma (HCC) ( 21 ), lung cancer ( 22 ), pancreatic neuroendocrine cancer(pNET) ( 23 ) and colorectal cancer(CRC) ( 24 ). In contrast, although HDAC5 was shown to induce tissue invasion of gastric cancer cells ( 25 ), gene expression profiles of histone modifiers indicate that HDAC5 is downregulated in gastric cancer ( 26 ) ( Table 1 ).…”

“…In neuroblastoma, HDAC5 promoted cell proliferation but had little effect on cell death ( 55 ). Overexpression of HDAC5 increased the proliferation of lung cancer cells, possibly via upregulation of downstream target genes ( 22 ). HDAC5 also increased DLL4 expression in colorectal cancer (CRC) cells, thereby enhancing their proliferation ( 57 ).…”

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“…Interacts with the promoter of FGF2 and SLIT2, downregulating endothelial cell growth [34] Represses angiogenesis by downregulating FGF2 and Slit2, resulting in reduced sprout formation [35] Colocalizes with YY1, maintaining a terminally-differentiated state in cardiomyocyte cells (H92C) [36] Represses transcription of cyclin D3 [37] Required for nuclear accumulation of HIF-1α in hypoxic conditions [38] Promotes proliferation of tumor cells [39] Leads to reduced glucose uptake in primary muscle cells (with reduction in GLUT4 (SLC2A4) gene but increased GLUT1 expression) and insulin-stimulated glycogen synthesis [40] 7…”