Inhibition of HDACs Suppresses Cell Proliferation and Cell Migration of Gastric Cancer by Regulating E2F5 Targeting BCL2

Abstract

(1) Background: Gastric cancer (GC) is the most common high death-rate cancer type worldwide, with an enhanced prevalence and increased rate of mortality. Although significant evidence on surgery strategy has been generated for the treatment of GC, conclusions are still uncertain regarding profound metastatic or persevering gastric cancer. Therefore, it is essential to develop novel and effective biomarkers or therapeutic targets for the diagnosis of GC. Histone deacetylations (HDACs) are important epigenetic regulators that control the aberrant transcription of critical genes that are mainly involved in cell proliferation, cell migration, regulation of the cell cycle, and different signal pathways. (2) Methods: Expression analysis of HDACs family members and E2F5 in gastric cancer cell lines was determined by RT-PCR and Western blotting. The cell proliferation was determined through an MTT assay. Cell migration was determined using a wound-healing assay. Flow cytometry experiments were used to determine cell-cycle analysis. The statistical software OriginPro 2015 (OriginLab, Northampton, MA, USA) was used to analyze data. A p value of < 0.05 was regarded as significant. (3) Results: The present study shows that E2F5 expression is upregulated in GC cancer cell lines compared to normal cell lines, and is positively associated with the level of HDACs and BCL2. HDACi and knocking down of E2F5 as tumor suppressors inhibited cell proliferation, migration invasion, and blocked the cell cycle in gastric cancer cells by suppressing BCL2. The results conclude that the anticancer mechanism of HDACi was determined by regulating E2F5 via targeting BCL2. (4) Conclusions: Our results suggest that the HDAC–E2F5–BCL2 signaling axis might be a novel potential biomarker in gastric cancer.

Histone Deacetylases Cooperate with NF-κB to Support the Immediate Migratory Response after Zebrafish Pronephros Injury

“…These differences to the murine model probably due to the differences in the windows of observation: the repair response via migration is immediate and takes place within minutes after injury. Suppressed migratory behavior upon HDAC inhibition has been previously described in various disease models, particularly in cancers [ 49 , 50 , 53 , 54 , 55 ]. For example, in human head and neck squamous cell carcinoma (HNSCC) and in colorectal cancer, TSA treatment inhibited cancer cell migration and invasiveness [ 53 , 54 ].…”

The HDAC2/YY1/c‐Myc signaling axis regulates lung cancer cell migration and proliferation

“…Increased HDACs function in human malignancies cause changes in the deacetylation of histones, resulting in structural abnormalities within nucleus. This can lead to suppression of genes that are crucial for cell differentiation and also inhibit abnormal cell proliferation, metastasis, and migration 9,10 . Recent studies reported that HDACs has been highly expressed in various human cancer including lung, thyroid, gastric, breast, colorectal, pancreatic, ovarian, brain, prostate, and in other types of hematological and solid tumor malignancies 11 .…”

“…This can lead to suppression of genes that are crucial for cell differentiation and also inhibit abnormal cell proliferation, metastasis, and migration. 9,10 Recent studies reported that HDACs has been highly expressed in various human cancer including lung, thyroid, gastric, breast, colorectal, pancreatic, ovarian, brain, prostate, and in other types of hematological and solid tumor malignancies. 11 Considering these, various studies concluded that the expression of HDACs was closely linked with increased proliferation, tumor dedifferentiation, invasion and migration, tumor stages, and patients' prognosis.…”

Targeting Class I Histone Deacetylases in Human Uterine Leiomyosarcoma

“…Its action is the opposite of histone acetyltransferase, which neutralizes their positive charge by acetylation of histone tails, thereby relaxing chromatin structure due to greater electrostatic repulsion from negatively charged DNA. Accumulated studies demonstrated that HDACs are involved in many biological events and pathological diseases [ 7 , 9 , 10 , 11 ], including varied types of cancer. Class I (HDACs 1, 2, 3, and 8) are located mainly in the nucleus and play an important role in cell proliferation, cell cycle progression, DNA damage response, development, and establishment and maintenance of the abnormal phenotype of diseases, including cancer progression [ 12 , 13 , 14 , 15 , 16 ].…”