Wang Ye, Xia Jufeng, Fang Zhaoyuan, Li Fei, Li Duo, Wang Zuoyun, Feng Yan, Zhang Jian, Chen Haiquan, Ji Hongbin, Liu Hongyan
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.
Oncotarget. 2017 May 16;8(20):33405-33415. doi: 10.18632/oncotarget.16796.
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.
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。