Functional identification of a novel transcript variant of INPP4B in human colon and breast cancer cells

Functional identification of a novel transcript variant of INPP4B in human colon and breast cancer cells
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DOI:
10.1016/j.bbrc.2017.02.012
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发表时间:
2017-03-25
影响因子:
3.1
通讯作者:
Jiang, Chen Chen
Jiang, Chen Chen
中科院分区:
生物学4区
文献类型:
--
作者:
Croft, Amanda;Guo, Su Tang;Jiang, Chen Chen

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4-磷酸肌醇多磷酸4-磷酸酶II(INPP 4 B)是P13 K信号通路的调节剂,其功能是根据细胞类型和环境抑制或促进下游激酶的活化。在这里,我们报告了一种新的小转录本变体INPP 4 B(INPP 4 B-S),在促进结肠癌和乳腺癌细胞增殖的作用的鉴定。INPP 4 B-S与全长INPP 4 B(INPP 4 B-FL)的不同之处在于在外显子15和16之间插入了一个小外显子,并缺失了外显子20-24。然而,1 NPP 4 B-S保留了INPP 4 B-FL的所有功能结构域,并且类似地位于细胞质中。在HCT 116和MCF-7细胞中,INPP 4 B-S的过表达增加,而INPP 4 B-S的选择性敲低降低了增殖速率。这些结果保证了进一步研究INPP 4 B-S在下游激酶活化和调节癌症发病机制中的作用。(C)2017爱思唯尔公司All rights reserved.
The 4-phosphatase Inositol polyphosphate 4-phosphatase II (INPP4B) is a regulator of the P13K signalling pathway and functions to suppress or promote activation of downstream kinases depending on cell type and context. Here we report the identification of a novel small transcript variant of INPP4B (INPP4B-S) that has a role in promoting proliferation of colon and breast cancer cells. INPP4B-S differed from full length INPP4B (INPP4B-FL) by the insertion of a small exon between exons 15 and 16 and the deletion of exons 20-24. Nevertheless, 1NPP4B-S retained all the functional domains of INPP4B-FL and was similarly located to the cytoplasm. Overexpression of INPP4B-S increased, whereas selective knockdown of INPP4B-S reduced the rate of proliferation in HCT116 and MCF-7 cells. These results warrant further investigation of the role INPP4B-S in activation of downstream kinases and in regulation of cancer pathogenesis. (C) 2017 Elsevier Inc. All rights reserved.