QKI5-mediated alternative splicing of the histone variant macroH2A1 regulates gastric carcinogenesis.
QKI5-mediated alternative splicing of the histone variant macroH2A1 regulates gastric carcinogenesis.
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QKI5介导的组蛋白变体macroH2A1的选择性剪接调节胃癌发生
DOI：
10.18632/oncotarget.8739
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发表时间：
2016-05-31
期刊：
影响因子：
--
通讯作者：
Yu J
中科院分区：
文献类型：
--
作者：
Li F;Yi P;Pi J;Li L;Hui J;Wang F;Liang A;Yu J
选择性的Pre-mRNA剪接是增加蛋白质组多样性和调控基因表达的关键机制。越来越多的证据表明，剪接程序在肿瘤发生过程中经常处于失调状态。癌细胞产生能促进生长和存活的蛋白质异构体。RNA结合蛋白QKI5是扩大人类原发肿瘤和肿瘤细胞系列表中选择性剪接的关键调节因子。然而，其在胃癌发生发展中的生物学作用和调控机制尚不清楚。在本研究中，我们证明了QKI5的下调与GC患者的pTNM分期和PM状态有关。再次导入QKI5可在体内外抑制胃癌细胞的增殖、迁移和侵袭，这可能是由于改变了宏H_2A1前-mRNA的剪接模式，导致了宏H_2A1.1亚型的积聚。此外，QKI5还可通过促进大分子H2A1.1的产生来抑制细胞周期蛋白L1的表达。因此，本研究确定了一个与胃肿瘤发生有关的新的调节轴，并为GC治疗提供了一种新的策略。
Alternative pre-mRNA splicing is a key mechanism for increasing proteomic diversity and modulating gene expression. Emerging evidence indicated that the splicing program is frequently dysregulated during tumorigenesis. Cancer cells produce protein isoforms that can promote growth and survival. The RNA-binding protein QKI5 is a critical regulator of alternative splicing in expanding lists of primary human tumors and tumor cell lines. However, its biological role and regulatory mechanism are poorly defined in gastric cancer (GC) development and progression. In this study, we demonstrated that the downregulation of QKI5 was associated with pTNM stage and pM state of GC patients. Re-introduction of QKI5 could inhibit GC cell proliferation, migration, and invasion in vitro and in vivo, which might be due to the altered splicing pattern of macroH2A1 pre-mRNA, leading to the accumulation of macroH2A1.1 isoform. Furthermore, QKI5 could inhibit cyclin L1 expression via promoting macroH2A1.1 production. Thus, this study identified a novel regulatory axis involved in gastric tumorigenesis and provided a new strategy for GC therapy.
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影响因子：
64.5
作者：
Hafner M;Landthaler M;Burger L;Khorshid M;Hausser J;Berninger P;Rothballer A;Ascano M Jr;Jungkamp AC;Munschauer M;Ulrich A;Wardle GS;Dewell S;Zavolan M;Tuschl T
通讯作者：
Tuschl T
影响因子：
3.6
作者：
Lu, Wei;Feng, Feixue;Lei, Xiaoying
通讯作者：
Lei, Xiaoying
影响因子：
4.6
作者：
Mitra, Sraboni;Mazumder (Indra), Dipanjana;Panda, Chinmay K.
通讯作者：
Panda, Chinmay K.
影响因子：
16
作者：
Anczuków O;Akerman M;Cléry A;Wu J;Shen C;Shirole NH;Raimer A;Sun S;Jensen MA;Hua Y;Allain FH;Krainer AR
通讯作者：
Krainer AR
QKI 缺乏会促进 FoxO1 介导的亚硝化应激和内质网应激，从而增加糖尿病心脏缺血性损伤的脆弱性。
影响因子：
5
作者：
Guo, Wangang;Jiang, Tiannan;Ma, Heng
通讯作者：
Ma, Heng