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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...

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Autores principales: Qin, Wang-Sen, Wu, Jin, Chen, Yang, Cui, Fa-Cai, Zhang, Fu-Ming, Lyu, Guan-Ting, Zhang, Hong-Mei
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
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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.
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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
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