The Short Isoform of Nuclear Mitotic Apparatus Protein 1 Functions as a Putative Tumor Suppressor.
The Short Isoform of Nuclear Mitotic Apparatus Protein 1 Functions as a Putative Tumor Suppressor.
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DOI：
10.4103/0366-6999.211535
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发表时间：
2017-08-05
影响因子：
6.1
通讯作者：
Zhang HM
中科院分区：
文献类型：
--
作者：
Qin WS;Wu J;Chen Y;Cui FC;Zhang FM;Lyu GT;Zhang HM
核有丝分裂器蛋白1（NuMA 1）具有长、中、短三种亚型，其中短NuMA亚型与长、中亚型相比具有明显的定位特征。然而，短NuMA在肿瘤形成过程中的作用尚不清楚。这项研究旨在揭示短NuMA在癌症发病机制中的作用。在配对的胃癌（GC）样品和不同的细胞系中探索短亚型的表达水平。此外，基于细胞增殖和细胞集落形成测定，短同种型表现为推定的肿瘤抑制因子。通过Pull-down分析和全基因组基因表达分析，寻找短NuMA的候选相互作用伴侣。短NuMA在细胞周期的S期和G2期高表达;与非肿瘤组织相比，短NuMA在9个GC中表达下调（GC1 [0.131，P = 5 × 10−4]; GC2 [0.316，P = 3 × 10−5]; GC3 [0.111，P = 6 × 10−4]; GC4 [0.456，P = 0.011]; GC5 [0.474，P = 0.001]; GC6 [0.311，P = 0.004]; GC 7 [0.28，P = 3 × 10−5]; GC 8 [0.298，P = 0.007];和GC 9 [0.344，P = 0.002]）。此外，短NuMA的高表达显著抑制细胞生长（2.43 × 105 vs. 2.97 × 105，P = 0.0029）和体外细胞克隆信息（70 vs. 2，P = 1.67 × 10−45）。短NuMA可以与α-辅肌动蛋白-4（ACTN 4）结合，ACTN 4是一种推定的肿瘤促进基因。短NuMA的过表达可使MYB原癌基因样2（MYBL 2）的表达显著降低约92倍，MYBL 2在细胞周期中起重要作用。短型NuMA可能具有抑癌作用。ACTN 4、MYBL 2与肿瘤进展的关系有待进一步研究。
Nuclear mitotic apparatus protein 1 (NuMA1) had been reported to produce three groups of isoforms categorized as long, middle, and short groups, of which short NuMA displayed distinct localization patterns compared to long and middle isoforms. However, the function of short NuMA was not clear in the progress of cancer formation. This study aimed to unveil the role of short NuMA in cancer pathogenesis. The expression levels of short isoforms were explored in paired gastric carcinoma (GC) samples and different cell lines. Furthermore, the short isoform behaved as a putative tumor suppressor based on cell proliferation and cell colony formation assays. Pull-down assay and whole-genome gene expression analysis were carried out to search candidate interaction partners of short NuMA. The expression of short NuMA was highly expressed in S and G2 phases of the cell cycle; compared with nontumor tissues, short NuMA downregulated in nine GCs (GC1 [0.131, P = 5 × 10−4]; GC2 [0.316, P = 3 × 10−5]; GC3 [0.111, P = 6 × 10−4]; GC4 [0.456, P = 0.011]; GC5 [0.474, P = 0.001]; GC6 [0.311, P = 0.004]; GC7 [0.28, P = 3 × 10−5]; GC8 [0.298, P = 0.007]; and GC9 [0.344, P = 0.002]). Besides, high expression of short NuMA significantly inhibits cell growth (2.43 × 105 vs. 2.97 × 105, P = 0.0029) and cell clone information in vitro (70 vs. 2, P = 1.67 × 10−45). Short NuMA could bind with alpha–actinin-4 (ACTN4), a putative tumor promoting gene. Overexpression of short NuMA could tremendously decrease the expression of MYB proto-oncogene like 2 (MYBL2) of about 92-fold, which played an important role in the cell cycles. Short isoform of NuMA might be functioned as a putative role of tumor suppressor. Further studies should be made to illuminate the relationship between ACTN4, MYBL2, and tumor progression.
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DOI：
10.1083/jcb.120.4.947
发表时间：
1993-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Compton DA;Cleveland DW
通讯作者：
Cleveland DW
DOI：
10.1083/jcb.116.6.1395
发表时间：
1992-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Compton DA;Szilak I;Cleveland DW
通讯作者：
Cleveland DW
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影响因子：
6.1
作者：
Liu K;Wang XJ;Li YN;Li B;Qi JS;Zhang J;Wang Y
通讯作者：
Wang Y
影响因子：
8
作者：
Bessa, M;Saville, MK;Watson, RJ
通讯作者：
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影响因子：
21.3
作者：
Siller, Karsten H.;Cabernard, Clemens;Doe, Chris Q.
通讯作者：
Doe, Chris Q.