The Short Isoform of Nuclear Mitotic Apparatus Protein 1 Functions as a Putative Tumor Suppressor  

作　　者：Wang-Sen Qin Jin Wu Yang Chen Fa-Cai Cui Fu-Ming Zhang Guan-Ting Lyu Hong-Mei Zhang 

机构地区：[1]Department of Clinical Laboratory, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, China [2]Department of Clinical Oncology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China [3]Central Laboratory, Haikou People's Hospital, Haikou, Hainan 570208, China [4]Department of Blood Transfusion, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China

出　　处：《Chinese Medical Journal》2017年第15期1824-1830,共7页中华医学杂志（英文版）

基　　金：This work was supported by grants from the National Natural Science Foundation （No. 81101490 and No. 81572699）.

摘　　要：Background：Nuclear mitotic apparatus protein 1 （NuMA 1） 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.Methods：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.Results：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 （GC 1 [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 × 10^-5 vs.2.97 × 10^-5,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.Conclusions：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.Background：Nuclear mitotic apparatus protein 1 （NuMA 1） 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.Methods：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.Results：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 （GC 1 [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 × 10^-5 vs.2.97 × 10^-5,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.Conclusions：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.

关 键 词：Cell Cycle Nuclear Mitotic Apparatus Protein 1 Short lsoform Tumor Suppressor 

分 类 号：Q78[生物学—分子生物学] Q253