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一种新型的BMX变体促进肺腺癌中肿瘤细胞的生长和迁移。

A novel BMX variant promotes tumor cell growth and migration in lung adenocarcinoma.

作者信息

Wang Ye, Xia Jufeng, Fang Zhaoyuan, Li Fei, Li Duo, Wang Zuoyun, Feng Yan, Zhang Jian, Chen Haiquan, Ji Hongbin, Liu Hongyan

机构信息

CAS Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai, 200031, China.

CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai, 200031, China.

出版信息

Oncotarget. 2017 May 16;8(20):33405-33415. doi: 10.18632/oncotarget.16796.

DOI:10.18632/oncotarget.16796
PMID:28422715
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5464877/
Abstract

The non-receptor tyrosine kinase BMX has been reported in several solid tumors. However, the alternative splicing of BMX and its clinical relevance in lung cancer remain to be elucidated. Exon1.0 array was used to identify a novel alternative splicing of BMX, BMXΔN, which was confirmed by rapid amplification of cDNA ends and reverse transcription-polymerase chain reaction. BMXΔN, resulting from exon skipping with excluding exon 1 to exon 8 of BMX gene, was found in 12% human lung adenocarcinoma specimens. BMXΔN is not found in paired pathologically normal lungs and positively correlated with EGFR mutation in lung adenocarcinomas. Moreover, BMXΔN increases cell proliferation, neoplastic transformation, and migratory property of human non-small cell lung cancer cells. The function of BMXΔN in lung cancer might be presumably due to enhanced ERK signaling.

摘要

非受体酪氨酸激酶BMX已在多种实体瘤中被报道。然而,BMX的可变剪接及其在肺癌中的临床相关性仍有待阐明。利用外显子1.0阵列鉴定出BMX的一种新型可变剪接体BMXΔN,通过cDNA末端快速扩增和逆转录-聚合酶链反应对其进行了验证。BMXΔN是由于BMX基因外显子1至外显子8缺失导致的外显子跳跃产生的,在12%的人肺腺癌标本中被发现。在配对的病理正常肺组织中未发现BMXΔN,且其与肺腺癌中的EGFR突变呈正相关。此外,BMXΔN可增加人非小细胞肺癌细胞的增殖、肿瘤转化和迁移特性。BMXΔN在肺癌中的功能可能是由于ERK信号增强所致。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efca/5464877/6d54c7cfaeaf/oncotarget-08-33405-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efca/5464877/885179c5c5de/oncotarget-08-33405-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efca/5464877/206c03dedcad/oncotarget-08-33405-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efca/5464877/c7f1be6607de/oncotarget-08-33405-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efca/5464877/15f8aa429ace/oncotarget-08-33405-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efca/5464877/d3a6675377aa/oncotarget-08-33405-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efca/5464877/6d54c7cfaeaf/oncotarget-08-33405-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efca/5464877/885179c5c5de/oncotarget-08-33405-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efca/5464877/206c03dedcad/oncotarget-08-33405-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efca/5464877/c7f1be6607de/oncotarget-08-33405-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efca/5464877/15f8aa429ace/oncotarget-08-33405-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efca/5464877/d3a6675377aa/oncotarget-08-33405-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efca/5464877/6d54c7cfaeaf/oncotarget-08-33405-g006.jpg

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本文引用的文献

1
RNA splicing factors as oncoproteins and tumour suppressors.作为癌蛋白和肿瘤抑制因子的RNA剪接因子
Nat Rev Cancer. 2016 Jul;16(7):413-30. doi: 10.1038/nrc.2016.51. Epub 2016 Jun 10.
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A splicing variant of Merlin promotes metastasis in hepatocellular carcinoma.Merlin的一种剪接变体促进肝细胞癌转移。
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Integrative genomic analysis reveals a high frequency of LKB1 genetic alteration in Chinese lung adenocarcinomas.整合基因组分析揭示中国肺腺癌中 LKB1 基因改变的高频率。
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Nonreceptor tyrosine kinase BMX maintains self-renewal and tumorigenic potential of glioblastoma stem cells by activating STAT3.非受体酪氨酸激酶 BMX 通过激活 STAT3 维持神经胶质瘤干细胞的自我更新和致瘤潜能。
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