Alternative transcription start site selection in ACSS2 controls its nuclear localization and promotes ribosome biosynthesis in hepatocellular carcinoma.
Alternative transcription start site selection in ACSS2 controls its nuclear localization and promotes ribosome biosynthesis in hepatocellular carcinoma.
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ACSS2 中的替代转录起始位点选择控制其核定位并促进肝细胞癌中的核糖体生物合成。
DOI：
10.1016/j.bbrc.2019.04.193
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发表时间：
2019-06
期刊：
影响因子：
--
通讯作者：
Jun Li
中科院分区：
文献类型：
--
作者：
Ya-Hui Wang;Shan Huang;Lei Zhu;Qin Yang;Xiao-Mei Yang;Jian-Ren Gu;Zhi-Gang Zhang;Hui-Zhen Nie;Jun Li
乙酰辅酶a合成酶2 （Acetyl-CoA synthetase 2, ACSS2）从乙酸酯中生成乙酰辅酶a，对组蛋白乙酰化和基因表达具有重要意义。ACSS2在肿瘤细胞中的位置不同，其功能也不同。ACSS2在肝细胞癌（HCC）中的作用和细胞定位仍有待研究。在此，我们发现ACSS2的替代转录起始位点选择在HCC和相应的邻近组织之间存在显著差异。替代转录起始位点选择产生了两个不同的ACSS2转录本，ACSS2- s1和ACSS2- s2。ACSS2的两个亚型具有不同的亚细胞定位和不同的功能。过表达ACSS2-S2可促进细胞增殖和侵袭，而过表达ACSS2-S1则无此作用。ACSS2-S1主要存在于细胞质中，而ACSS2-S2在细胞核和细胞质中均有分布。最后，我们证明了ACSS2的替代转录起始位点选择与HCC中核糖体的生物发生有关。我们的研究结果揭示了ACSS2-S2通过增加核糖体生物发生在HCC进展中的致癌作用，并提示ACSS2-S2可能是HCC的潜在治疗靶点。
Acetyl-CoA synthetase 2 (ACSS2) generates acetyl-CoA from acetate is important for histone acetylation and gene expression. ACSS2 fulfills distinct functions depending on its cellular location in tumor cells. The role and cellular localization of ACSS2 in hepatocellular carcinoma (HCC) remains to be studied. Herein, we identified that the alternative transcription start site selection of ACSS2 was significantly different between HCC and corresponding adjacent tissues. Alternative transcription start site selection produced two different ACSS2 transcripts, ACSS2-S1 and ACSS2-S2. The two isoforms of ACSS2 had different subcellular localization and different functions. Overexpression of ACSS2-S2 promoted cell proliferation and invasion, but ACSS2-S1 did not. The ACSS2-S1 was mainly present in cytoplasm, and ACSS2-S2 was distributed in both nucleus and cytoplasm. Finally, we demonstrated that alternative transcription start site selection of ACSS2 correlates ribosome biogenesis in HCC. Our findings reveal an oncogenic role of ACSS2-S2 in HCC progression via increase of ribosome biogenesis, and suggest ACSS2-S2 might be a potential therapeutic target against the HCC.
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影响因子：
2.2
作者：
Song, Myeong Jun;Jung, Chan Kwon;Yoon, Seung Kew
通讯作者：
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影响因子：
64.8
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影响因子：
4.8
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通讯作者：
Li, E
影响因子：
1.7
作者：
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