Global effect of inauhzin on human p53-responsive transcriptome.
Previously, we reported that Inauhzin (INZ) induces p53 activity and suppresses tumor growth by inhibiting Sirt1. However, it remains unknown whether INZ may globally affect p53-dependent gene expression or not. Herein, we have conducted microarray and real-time PCR analyses of gene expression to de...
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doaj-3deccde566704fa18e9d11aa5688de092020-11-25T01:17:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01712e5217210.1371/journal.pone.0052172Global effect of inauhzin on human p53-responsive transcriptome.Jun-Ming LiaoShelya X ZengXiang ZhouHua LuPreviously, we reported that Inauhzin (INZ) induces p53 activity and suppresses tumor growth by inhibiting Sirt1. However, it remains unknown whether INZ may globally affect p53-dependent gene expression or not. Herein, we have conducted microarray and real-time PCR analyses of gene expression to determine the global effect of INZ on human p53-responsive transcriptome.In this study, we conducted microarray analysis followed by PCR validation of general gene expression in HCT116(p53+/+) and HCT116(p53-/-) cells treated with or without INZ. Microarray data showed that 324 genes were up-regulated by ≥ 2.3-fold and 266 genes were down-regulated by ≥ 2-fold in response to INZ treatment in a p53-dependent manner. GO analysis for these genes further revealed that INZ affects several biological processes, including apoptosis (GO:0006915), cell cycle (GO:0007049), immune system process (GO:0002376), and cell adhesion (GO:0007155), which are in line with p53 functions in cells. Also, pathway and STRING analyses of these genes indicated that the p53-signaling pathway is the most significant pathway responsive to INZ treatment as predicted, since a number of these p53 target genes have been previously reported and some of them were validated by RT-qPCR. Finally, among the 9 tested and highly expressed genes, ACBD4, APOBEC3C, and FLJ14327 could be novel p53 target genes, for they were up-regulated by INZ in HCT116(p53+/+) cells, but not in HCT116(p53-/-) cells.From our whole genome microarray analysis followed by validation with RT-qPCR, we found that INZ can indeed induce the expression of p53 target genes at a larger scale or globally. Our findings not only verify that INZ indeed activates the p53 signaling pathway, but also provide useful information for identifying novel INZ and/or p53 targets. The global effect of INZ on human p53-responsive transcriptome could also be instrumental to the future design of INZ clinical trials.http://europepmc.org/articles/PMC3528779?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jun-Ming Liao Shelya X Zeng Xiang Zhou Hua Lu |
spellingShingle |
Jun-Ming Liao Shelya X Zeng Xiang Zhou Hua Lu Global effect of inauhzin on human p53-responsive transcriptome. PLoS ONE |
author_facet |
Jun-Ming Liao Shelya X Zeng Xiang Zhou Hua Lu |
author_sort |
Jun-Ming Liao |
title |
Global effect of inauhzin on human p53-responsive transcriptome. |
title_short |
Global effect of inauhzin on human p53-responsive transcriptome. |
title_full |
Global effect of inauhzin on human p53-responsive transcriptome. |
title_fullStr |
Global effect of inauhzin on human p53-responsive transcriptome. |
title_full_unstemmed |
Global effect of inauhzin on human p53-responsive transcriptome. |
title_sort |
global effect of inauhzin on human p53-responsive transcriptome. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2012-01-01 |
description |
Previously, we reported that Inauhzin (INZ) induces p53 activity and suppresses tumor growth by inhibiting Sirt1. However, it remains unknown whether INZ may globally affect p53-dependent gene expression or not. Herein, we have conducted microarray and real-time PCR analyses of gene expression to determine the global effect of INZ on human p53-responsive transcriptome.In this study, we conducted microarray analysis followed by PCR validation of general gene expression in HCT116(p53+/+) and HCT116(p53-/-) cells treated with or without INZ. Microarray data showed that 324 genes were up-regulated by ≥ 2.3-fold and 266 genes were down-regulated by ≥ 2-fold in response to INZ treatment in a p53-dependent manner. GO analysis for these genes further revealed that INZ affects several biological processes, including apoptosis (GO:0006915), cell cycle (GO:0007049), immune system process (GO:0002376), and cell adhesion (GO:0007155), which are in line with p53 functions in cells. Also, pathway and STRING analyses of these genes indicated that the p53-signaling pathway is the most significant pathway responsive to INZ treatment as predicted, since a number of these p53 target genes have been previously reported and some of them were validated by RT-qPCR. Finally, among the 9 tested and highly expressed genes, ACBD4, APOBEC3C, and FLJ14327 could be novel p53 target genes, for they were up-regulated by INZ in HCT116(p53+/+) cells, but not in HCT116(p53-/-) cells.From our whole genome microarray analysis followed by validation with RT-qPCR, we found that INZ can indeed induce the expression of p53 target genes at a larger scale or globally. Our findings not only verify that INZ indeed activates the p53 signaling pathway, but also provide useful information for identifying novel INZ and/or p53 targets. The global effect of INZ on human p53-responsive transcriptome could also be instrumental to the future design of INZ clinical trials. |
url |
http://europepmc.org/articles/PMC3528779?pdf=render |
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