Panobinostat reverses HepaCAM gene expression and suppresses proliferation by increasing histone acetylation in prostate cancer

DU145型 全景望远镜 生物 LNCaP公司 癌症研究 乙酰化 组蛋白 组蛋白H4 组蛋白脱乙酰基酶 H3K4me3 分子生物学 基因表达 前列腺癌 癌症 生物化学 发起人 遗传学 基因
作者
E Chen,Nanjing Liu,Yan Zhao,Min Tang,Liping Ou,Xiaohou Wu,Chunli Luo
出处
期刊:Gene [Elsevier]
卷期号:808: 145977-145977 被引量:4
标识
DOI:10.1016/j.gene.2021.145977
摘要

Increased expression of histone deacetylases (HDACs) affiliated to the epigenetic regulation is common aberration in prostate cancer (PCa). We have confirmed that hepatocyte cell adhesion molecule (hepaCAM), acting as a tumor suppressor gene, is rarely expressed in PCa previously, However, the mechanisms of which is still unknown. The level of histone acetylation reportedly may involve anti-oncogene transcription and expression. In this study, we investigated the effect of panobinostat, the broad-spectrum histone deacetylases inhibitor, on PCa LNCaP and DU145 cell growth, and observed re-expression of hepaCAM when treated with panobinostat. We demonstrated that intranuclear acetylation of lys9 of histone H3 (Ac-H3K9) were increased, while that of both mRNA and protein of HDAC1, HDAC3, and HDAC4 were decreased when the treating concentration of panobinostat increased. We confirmed the relationship between histone acetylation and the expression of hepaCAM and AR in prostate cancer tissues. We also confirmed that panobinostat could overcome the resistance for androgen deprivation therapy (ADT). Further, we combined panobinostat with Ad-hepaCAM, which resulted in significantly increased antitumor activity and significant attenuation of the proliferation-associated genes CCND1 and PCNA compared to each single treatment. In conclusion, panobinostat may enhance the acetylation of lys9 of histone 3 and reverse the hepaCAM expression through its inhibitory effect on HDACs activity in PCa LNCaP and DU145 cells; Ad-hepaCAM combined with panobinostat may synergistically inhibit the growth of LNCaP and DU145 cells, via a potential mechanism associated with the down-regulation of the expression of CCND1 and PCNA. These findings suggest that this therapeutic strategy should be further developed in clinical trials.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
Yanzhi发布了新的文献求助10
刚刚
坤坤发布了新的文献求助10
刚刚
西瓜瓜发布了新的文献求助10
1秒前
神经脊柱与周围神经完成签到,获得积分10
1秒前
六氟合铂酸氙应助半山采纳,获得20
1秒前
Queen发布了新的文献求助10
2秒前
2秒前
桐桐应助zakarya采纳,获得10
2秒前
2秒前
3秒前
3秒前
小竹子发布了新的文献求助10
3秒前
3秒前
时尚的画笔完成签到,获得积分10
3秒前
海智发布了新的文献求助20
4秒前
6秒前
tu123完成签到,获得积分10
6秒前
6秒前
打打应助LemonFish采纳,获得10
7秒前
super chan发布了新的文献求助10
7秒前
zhang发布了新的文献求助10
8秒前
英俊的铭应助自由冰凡采纳,获得10
8秒前
8秒前
59完成签到 ,获得积分10
8秒前
8秒前
8秒前
9秒前
VDC发布了新的文献求助10
9秒前
不可思宇发布了新的文献求助10
9秒前
科研通AI5应助勤恳的书文采纳,获得200
10秒前
mpbio完成签到,获得积分10
10秒前
西瓜瓜完成签到,获得积分10
11秒前
stonerbai完成签到,获得积分10
12秒前
xiaofanfan完成签到,获得积分10
12秒前
李健的粉丝团团长应助Faiz采纳,获得10
12秒前
Sunlty完成签到,获得积分10
12秒前
何欢完成签到,获得积分10
13秒前
ano发布了新的文献求助10
13秒前
我是老大应助冷艳中蓝采纳,获得10
13秒前
jie367发布了新的文献求助10
13秒前
高分求助中
Production Logging: Theoretical and Interpretive Elements 2700
Conference Record, IAS Annual Meeting 1977 1050
Les Mantodea de Guyane Insecta, Polyneoptera 1000
England and the Discovery of America, 1481-1620 600
Teaching language in context (Third edition) by Derewianka, Beverly; Jones, Pauline 550
Typology of Conditional Constructions 500
Plant–Pollinator Interactions: From Specialization to Generalization 400
热门求助领域 (近24小时)
化学 材料科学 生物 医学 工程类 有机化学 生物化学 物理 纳米技术 计算机科学 内科学 化学工程 复合材料 基因 遗传学 物理化学 催化作用 量子力学 光电子学 冶金
热门帖子
关注 科研通微信公众号,转发送积分 3588129
求助须知:如何正确求助?哪些是违规求助? 3156736
关于积分的说明 9512078
捐赠科研通 2859631
什么是DOI,文献DOI怎么找? 1571486
邀请新用户注册赠送积分活动 737091
科研通“疑难数据库(出版商)”最低求助积分说明 722083