LMX1A inhibits C-Myc expression through ANGPTL4 to exert tumor suppressive role in gastric cancer.
Our research group has showed that the LIM homeobox transcription factor 1 alpha (LMX1A) is inactivated in gastric cancers. Overexpression of LMX1A inhibits tumor growth. However, the mechanisms remains unclear. Considering LMX1A as a transcription factor, a comparison of RNA-seq between gastric can...
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doaj-ae74b974aeb64056bd131788e8c895432021-03-03T21:12:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01149e022164010.1371/journal.pone.0221640LMX1A inhibits C-Myc expression through ANGPTL4 to exert tumor suppressive role in gastric cancer.Peiyu QianJian LiXiaohong ZhangFan LiSonghua BeiHuanqing LiQi SunLi FengOur research group has showed that the LIM homeobox transcription factor 1 alpha (LMX1A) is inactivated in gastric cancers. Overexpression of LMX1A inhibits tumor growth. However, the mechanisms remains unclear. Considering LMX1A as a transcription factor, a comparison of RNA-seq between gastric cancer cells (GCCs) and GCCs with LMX1A overexpressed was performed to identify genes transcriptionally activated by LMX1A. Among the potential LMX1A target genes, angiopoietin-like 4 (ANGPTL4) has been reported to be an important tumor suppressor and thus was selected for further validation and research. Both LMX1A and ANGPTL4 showed downregulated expression in gastric cancer samples. More importantly, the expression of LMX1A is positively correlated with ANGPTL4, without including other family members in gastric cancer cell lines. What's more, knockdown of ANGPTL4 rescued the tumor suppressive phenotype of LMX1A overexpression, which indicated that LMX1A upregulates ANGPTL4 to exert its role. Mechanistically, we found that LMX1A inhibited the expression of the oncogene C-Myc, which is alleviated by ANGPTL4 knockdown. In general, our results showed that LMX1A exerts its tumor suppressive role by activating ANGPTL4 to inhibit C-Myc.https://doi.org/10.1371/journal.pone.0221640 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Peiyu Qian Jian Li Xiaohong Zhang Fan Li Songhua Bei Huanqing Li Qi Sun Li Feng |
spellingShingle |
Peiyu Qian Jian Li Xiaohong Zhang Fan Li Songhua Bei Huanqing Li Qi Sun Li Feng LMX1A inhibits C-Myc expression through ANGPTL4 to exert tumor suppressive role in gastric cancer. PLoS ONE |
author_facet |
Peiyu Qian Jian Li Xiaohong Zhang Fan Li Songhua Bei Huanqing Li Qi Sun Li Feng |
author_sort |
Peiyu Qian |
title |
LMX1A inhibits C-Myc expression through ANGPTL4 to exert tumor suppressive role in gastric cancer. |
title_short |
LMX1A inhibits C-Myc expression through ANGPTL4 to exert tumor suppressive role in gastric cancer. |
title_full |
LMX1A inhibits C-Myc expression through ANGPTL4 to exert tumor suppressive role in gastric cancer. |
title_fullStr |
LMX1A inhibits C-Myc expression through ANGPTL4 to exert tumor suppressive role in gastric cancer. |
title_full_unstemmed |
LMX1A inhibits C-Myc expression through ANGPTL4 to exert tumor suppressive role in gastric cancer. |
title_sort |
lmx1a inhibits c-myc expression through angptl4 to exert tumor suppressive role in gastric cancer. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2019-01-01 |
description |
Our research group has showed that the LIM homeobox transcription factor 1 alpha (LMX1A) is inactivated in gastric cancers. Overexpression of LMX1A inhibits tumor growth. However, the mechanisms remains unclear. Considering LMX1A as a transcription factor, a comparison of RNA-seq between gastric cancer cells (GCCs) and GCCs with LMX1A overexpressed was performed to identify genes transcriptionally activated by LMX1A. Among the potential LMX1A target genes, angiopoietin-like 4 (ANGPTL4) has been reported to be an important tumor suppressor and thus was selected for further validation and research. Both LMX1A and ANGPTL4 showed downregulated expression in gastric cancer samples. More importantly, the expression of LMX1A is positively correlated with ANGPTL4, without including other family members in gastric cancer cell lines. What's more, knockdown of ANGPTL4 rescued the tumor suppressive phenotype of LMX1A overexpression, which indicated that LMX1A upregulates ANGPTL4 to exert its role. Mechanistically, we found that LMX1A inhibited the expression of the oncogene C-Myc, which is alleviated by ANGPTL4 knockdown. In general, our results showed that LMX1A exerts its tumor suppressive role by activating ANGPTL4 to inhibit C-Myc. |
url |
https://doi.org/10.1371/journal.pone.0221640 |
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