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| Status |
Public on Aug 18, 2017 |
| Title |
4β-Hydroxywithanolide E Modulates Alternative Splicing of Apoptotic Genes in Human Hepatocellular Carcinoma Huh-7 Cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Alternative splicing is a mechanism for increasing the protein variety of a limited number of genes. Studies have shown that aberrant regulations of the alternative splicing of apoptotic gene transcripts may contribute to the development of cancer. In this study, we isolated 4β-Hydroxywithanolide E (4bHWE) from the traditional herb Physalis peruviana, and analyzed its biological effects in cancer cells. The results demonstrated that 4bHWE modulates the alternative splicing of apoptotic genes (e.g., HIPK3, SMAC/DIABLO, and SURVIVIN), changes the expression level of splicing factors (e.g., hnRNP C1/C2, ASF/SF2, SRp20, and SRp55), and induces histone tail posttranslational modifications (e.g., H3K27me1, H3K27me2, H3K36me3, and H3K79me1). Pretreatment with okadaic acid to inhibit protein phosphatase-1 could partly relieve the effects of 4bHWE on the alternative splicing of HIPK3 and SMAC/DIABLO transcripts, as well as on the dephosphorylation of ASF/SF2. Genome-wide detection of alternative splicing further indicated that several other apoptosis-related genes are also regulated by 4bHWE, including APAF1, CARP-1, and RIPK1. Moreover, we extended our study to apoptosis-associated molecules, detecting an increasing level of CASPASE-3 activity and cleavage of poly ADP-ribose polymerase in 4bHWE-induced apoptosis. Furthermore, in vivo experiments showed that the treatment of tumor-bearing mice with 4bHWE resulted in a marked decrease of tumor size and weight. Taken together, this study is the first to show that 4bHWE affects alternative splicing through the modulations of splicing factors, providing a novel view of the antitumor mechanism of 4bHWE.
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| Overall design |
Examination of the global genes with altered alternative splicing in 4bHWE-treated Huh-7 cells.
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| Contributor(s) |
Chang J, Lee C |
| Citation(s) |
28779122 |
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| Submission date |
Apr 04, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Chien Chih Lee |
| E-mail(s) |
insect@hotmail.com.tw
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| Organization name |
China Medical University Hospital
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| Lab |
Epigenome Research Center
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| Street address |
2 Yuh-Der Road
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| City |
Taichung |
| ZIP/Postal code |
404 |
| Country |
Taiwan |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA317320 |
| SRA |
SRP072880 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE79884_RAW.tar |
6.2 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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