Cargando…
The Short Isoform of Nuclear Mitotic Apparatus Protein 1 Functions as a Putative Tumor Suppressor
BACKGROUND: 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...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Medknow Publications & Media Pvt Ltd
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5547835/ https://www.ncbi.nlm.nih.gov/pubmed/28748856 http://dx.doi.org/10.4103/0366-6999.211535 |
_version_ | 1783255742990516224 |
---|---|
author | Qin, Wang-Sen Wu, Jin Chen, Yang Cui, Fa-Cai Zhang, Fu-Ming Lyu, Guan-Ting Zhang, Hong-Mei |
author_facet | Qin, Wang-Sen Wu, Jin Chen, Yang Cui, Fa-Cai Zhang, Fu-Ming Lyu, Guan-Ting Zhang, Hong-Mei |
author_sort | Qin, Wang-Sen |
collection | PubMed |
description | BACKGROUND: 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. 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 (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 × 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. |
format | Online Article Text |
id | pubmed-5547835 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Medknow Publications & Media Pvt Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-55478352017-08-21 The Short Isoform of Nuclear Mitotic Apparatus Protein 1 Functions as a Putative Tumor Suppressor Qin, Wang-Sen Wu, Jin Chen, Yang Cui, Fa-Cai Zhang, Fu-Ming Lyu, Guan-Ting Zhang, Hong-Mei Chin Med J (Engl) Original Article BACKGROUND: 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. 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 (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 × 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. Medknow Publications & Media Pvt Ltd 2017-08-05 /pmc/articles/PMC5547835/ /pubmed/28748856 http://dx.doi.org/10.4103/0366-6999.211535 Text en Copyright: © 2017 Chinese Medical Journal http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. |
spellingShingle | Original Article Qin, Wang-Sen Wu, Jin Chen, Yang Cui, Fa-Cai Zhang, Fu-Ming Lyu, Guan-Ting Zhang, Hong-Mei The Short Isoform of Nuclear Mitotic Apparatus Protein 1 Functions as a Putative Tumor Suppressor |
title | The Short Isoform of Nuclear Mitotic Apparatus Protein 1 Functions as a Putative Tumor Suppressor |
title_full | The Short Isoform of Nuclear Mitotic Apparatus Protein 1 Functions as a Putative Tumor Suppressor |
title_fullStr | The Short Isoform of Nuclear Mitotic Apparatus Protein 1 Functions as a Putative Tumor Suppressor |
title_full_unstemmed | The Short Isoform of Nuclear Mitotic Apparatus Protein 1 Functions as a Putative Tumor Suppressor |
title_short | The Short Isoform of Nuclear Mitotic Apparatus Protein 1 Functions as a Putative Tumor Suppressor |
title_sort | short isoform of nuclear mitotic apparatus protein 1 functions as a putative tumor suppressor |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5547835/ https://www.ncbi.nlm.nih.gov/pubmed/28748856 http://dx.doi.org/10.4103/0366-6999.211535 |
work_keys_str_mv | AT qinwangsen theshortisoformofnuclearmitoticapparatusprotein1functionsasaputativetumorsuppressor AT wujin theshortisoformofnuclearmitoticapparatusprotein1functionsasaputativetumorsuppressor AT chenyang theshortisoformofnuclearmitoticapparatusprotein1functionsasaputativetumorsuppressor AT cuifacai theshortisoformofnuclearmitoticapparatusprotein1functionsasaputativetumorsuppressor AT zhangfuming theshortisoformofnuclearmitoticapparatusprotein1functionsasaputativetumorsuppressor AT lyuguanting theshortisoformofnuclearmitoticapparatusprotein1functionsasaputativetumorsuppressor AT zhanghongmei theshortisoformofnuclearmitoticapparatusprotein1functionsasaputativetumorsuppressor AT qinwangsen shortisoformofnuclearmitoticapparatusprotein1functionsasaputativetumorsuppressor AT wujin shortisoformofnuclearmitoticapparatusprotein1functionsasaputativetumorsuppressor AT chenyang shortisoformofnuclearmitoticapparatusprotein1functionsasaputativetumorsuppressor AT cuifacai shortisoformofnuclearmitoticapparatusprotein1functionsasaputativetumorsuppressor AT zhangfuming shortisoformofnuclearmitoticapparatusprotein1functionsasaputativetumorsuppressor AT lyuguanting shortisoformofnuclearmitoticapparatusprotein1functionsasaputativetumorsuppressor AT zhanghongmei shortisoformofnuclearmitoticapparatusprotein1functionsasaputativetumorsuppressor |