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| Status |
Public on Jun 10, 2019 |
| Title |
CRKL regulates alternative splicing of genes that function in tumorigenesis and cancer progression |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
CRKL adaptor protein was demonstrated to have important effects in various types of human cancer and contributes to malignant cell growth and chemoresistance as an overexpressed oncoprotein in cervical carcinoma. But the special molecular mechanisms of CRKL in cervical cancer remain unknown. Here we reported that CRKL regulates genes in cervical cancer related pathways via targeting alternative splicing. We analyzed the expression level of CRKL in 300 cervical cancer tissue samples available in TCGA database, showing a significant increase expression in Stage I cancer samples. From these tumor samples, we selected 40 cancer samples with 20 showing high CRKL expression and 20 showing low, which were analyzed for the potential impact of CRKL on alternative splicing regulation of cancer transcriptome. We further explored the potential function of CRKL in promoting cell proliferation and regulating alternative splicing in HeLa cells using shRNA to knock-down CRKL expression. More importantly, we showed that 34 (94%) of CRKL-regulated alternative splicing events detected in HeLa cells could be validated by qPCR approach and more than a half of these validated events detected in HeLa cells were also correlated with the CRKL expression level in cervical cancers. These results together support a conclusion that CRKL adaptor protein extensively regulates alternative splicing of many genes which are important in tumorigenesis and cancer progression, which expands the functional importance of signaling adaptors in coordinating the dynamic activation of signaling pathways with cellular responses at the alternative splicing level.
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| Overall design |
transcrptional analysis of CRKL knockdown and control in Hela cells
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| Contributor(s) |
Song Q |
| Citation(s) |
31133010 |
| Submission date |
Sep 28, 2018 |
| Last update date |
Jun 10, 2019 |
| Contact name |
Dong Chen |
| Organization name |
ABLife, Inc.
|
| Department |
Center for Genome Analysis
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| Street address |
388 GaoXin 2nd Road, East Lake Hi-Tech Development Zone
|
| City |
Wuhan |
| State/province |
Hubei |
| ZIP/Postal code |
430075 |
| Country |
China |
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| Platforms (1) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA495833 |
| SRA |
SRP165216 |
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