Histone deacetylase 3 promotes pancreatic cancer cell proliferation, invasion and increases drug-resistance through histone modification of P27, P53 and Bax
Histone deacetylase 3 promotes pancreatic cancer cell proliferation, invasion and increases drug-resistance through histone modification of P27, P53 and Bax
复制标题
组蛋白脱乙酰酶 3 通过 P27、P53 和 Bax 的组蛋白修饰促进胰腺癌细胞增殖、侵袭并增加耐药性。
DOI：
10.3892/ijo.2014.2568
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发表时间：
2014-10-01
影响因子：
5.2
通讯作者：
Wang, Lei
中科院分区：
文献类型：
--
作者：
Jiao, Feng;Hu, Hai;Wang, Lei
胰腺癌是最具侵袭性的实体恶性肿瘤之一，生存率低。最近的研究表明，组蛋白去乙酰化酶3（HDAC 3）的高表达水平与恶性表型相关。然而，HDAC3在胰腺癌中的表达模式和生物学作用仍不清楚。在这项研究中，我们的数据表明，HDAC3蛋白表达水平较高，胰腺癌相比，配对癌旁组织。HDAC3在8株胰腺癌细胞系中的表达水平均高于人胰腺导管上皮细胞（HPDE）。此外，进一步的功能分析显示HDAC3可作为致癌蛋白发挥作用，促进胰腺癌细胞的增殖、迁移和侵袭，并可能增加耐药性。此外，HDAC3的功能参与部分与诱导后抑制P53，P27和Bax基因转录，通过H3K9脱乙酰化作用。总之，我们的数据表明HDAC3通过组蛋白修饰参与胰腺癌的发病和进展，这可能是对抗这种毁灭性疾病的关键表观遗传靶点。
Pancreatic cancer is one of the most aggressive solid malignancies with a dismal survival rate. Recent studies have shown that high expression levels of histone deacetylase 3 (HDAC3) correlate with malignant phenotype. However, the expression patterns and biological role of HDAC3 in pancreatic cancer remain unclear. In this study, our data showed that a higher level of HDAC3 protein expression was found in pancreatic cancer as compared to paired paracancerous tissues. Consistently, higher expression level of HDAC3 was found in all of the eight pancreatic cancer cell lines relative to human pancreatic ductal epithelial cells (HPDE). In addition, further function analysis revealed that HDAC3 can function as oncogenic protein, which could promote pancreatic cancer cell proliferation, migration and invasion, and may increase drug resistance. Moreover, the functional involvement of HDAC3 was partially correlated with post-induction repression of P53, P27 and Bax gene transcription, acting via H3K9 deacetylation. Taken together, our data suggest that HDAC3 participates in the pathogenesis and progression of pancreatic cancer through histone modification, which might be a pivotal epigenetic target against this devastating disease.