Histone deacetylase 3 promotes liver regeneration and liver cancer cells proliferation through signal transducer and activator of transcription 3 signaling pathway.
Histone deacetylase 3 promotes liver regeneration and liver cancer cells proliferation through signal transducer and activator of transcription 3 signaling pathway.
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组蛋白脱乙酰酶 3 通过信号转导器和转录 3 信号通路激活剂促进肝脏再生和肝癌细胞增殖。
DOI：
10.1038/s41419-018-0428-x
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发表时间：
2018-03-14
影响因子：
9
通讯作者：
Bu H
中科院分区：
文献类型：
--
作者：
Lu XF;Cao XY;Zhu YJ;Wu ZR;Zhuang X;Shao MY;Xu Q;Zhou YJ;Ji HJ;Lu QR;Shi YJ;Zeng Y;Bu H
组蛋白去乙酰化酶3 （HDAC3）在细胞周期调节中起关键作用，在包括肝细胞癌（HCC）在内的多种癌症中经常异常表达，但对其在肝脏再生和肝癌细胞增殖中的作用知之甚少。使用可诱导的肝细胞选择性HDAC3敲除小鼠，我们发现缺乏HDAC3会显著损害肝脏再生并阻断G1期进入的肝细胞增殖。HDAC3失活严重破坏了转录3 （STAT3）级联的信号传感器和激活子。HDAC3沉默会破坏细胞质中ac-STAT3到p-STAT3的转化，导致STAT3信号传导的破坏。此外，HDAC3过表达与HCC患者肿瘤生长增加和预后不良进一步相关。抑制HDAC3表达可降低肝癌细胞生长，抑制异种移植瘤生长。我们的研究结果表明，HDAC3是肝再生和癌症中stat3依赖性细胞增殖的重要调节因子。这些发现为HDAC3-STAT3通路在肝脏病理生理过程中的作用提供了新的见解。
Histone deacetylase 3 (HDAC3) plays pivotal roles in cell cycle regulation and is often aberrantly expressed in various cancers including hepatocellular carcinoma (HCC), but little is known about its role in liver regeneration and liver cancer cells proliferation. Using an inducible hepatocyte-selective HDAC3 knockout mouse, we find that lack of HDAC3 dramatically impaired liver regeneration and blocked hepatocyte proliferation in the G1 phase entry. HDAC3 inactivation robustly disrupted the signal transducer and activator of transcription 3 (STAT3) cascade. HDAC3 silencing impaired the ac-STAT3-to-p-STAT3 transition in the cytoplasm, leading to the subsequent breakdown of STAT3 signaling. Furthermore, overexpressed HDAC3 was further associated with increased tumor growth and a poor prognosis in HCC patients. Inhibition of HDAC3 expression reduced liver cancer cells growth and inhibited xenograft tumor growth. Our results suggest that HDAC3 is an important regulator of STAT3-dependent cell proliferation in liver regeneration and cancer. These findings provide novel insights into the HDAC3–STAT3 pathway in liver pathophysiological processes.
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影响因子：
10.5
作者：
Li, Yun;Kao, Gary D.;Lazar, Mitchell A.
通讯作者：
Lazar, Mitchell A.
影响因子：
4.8
作者：
Gao, ZG;He, Q;Ye, JP
通讯作者：
Ye, JP
影响因子：
2.7
作者：
Farooq, Muhammad;Sulochana, K. N.;Ge, Ruowen
通讯作者：
Ge, Ruowen
影响因子：
4.1
作者：
Li, Dongmin;Wang, Xuan;Lu, Shemin
通讯作者：
Lu, Shemin
影响因子：
50.3
作者：
Bhaskara S;Knutson SK;Jiang G;Chandrasekharan MB;Wilson AJ;Zheng S;Yenamandra A;Locke K;Yuan JL;Bonine-Summers AR;Wells CE;Kaiser JF;Washington MK;Zhao Z;Wagner FF;Sun ZW;Xia F;Holson EB;Khabele D;Hiebert SW
通讯作者：
Hiebert SW