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| Status |
Public on Mar 22, 2009 |
| Title |
Protein Kinase C Alpha Promotes Tumor Growth by Initiating a Feed-forward Network Involving miR-15a and Cyclin E |
| Platform organisms |
Homo sapiens; Mus musculus; Rattus norvegicus |
| Sample organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by array
|
| Summary |
Protein Kinase C alpha (PKC) is associated with progression and poor prognosis in head and neck cancer. Previous studies have demonstrated that PKC sustains the proliferative signal by increasing cyclin E expression, leading to enhanced E2F target gene transcription and DNA synthesis. Here we show that PKC increases DNA synthesis through inhibition of the microRNA, miR-15a, upregulating translation of its target cyclin E. Importantly, gene expression and qRT-PCR analysis of primary squamous cell carcinoma tumors of the head and neck (SCCHN) reveals a significant negative correlation between PKC alpha and miR-15a levels. In contrast to normal cell cycle initiation, PKC decreases microRNA expression, leading first to increased cyclin E protein followed by enhanced transcription of cyclin E and other DNA synthesis mediators. These results identify a signaling network regulated by PKC whereby constitutive kinase activation switches the system to feed forward, overriding normal regulation of cell cycle progression through a post-transcriptional mechanism involving microRNAs. This reprogramming of the network is likely a more general phenomenon that can account for the oncogenic potency of established signaling pathways.
Keywords: miRNA; dose response; cancer
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| |
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| Overall design |
6 treated samples across two time points hybridized to paired time 0, untreated controls
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| |
|
| Contributor(s) |
Chung CH, Parker JS |
| Citation(s) |
19117988 |
| Submission date |
Jan 28, 2008 |
| Last update date |
Apr 19, 2012 |
| Contact name |
Christine H. Chung |
| E-mail(s) |
christine.chung@vanderbilt.edu
|
| Phone |
615-322-4967
|
| Fax |
615343-7602
|
| Organization name |
Vanderbilt University
|
| Department |
Internal Medicine
|
| Lab |
Chung
|
| Street address |
777 PRB
|
| City |
Nashville |
| State/province |
TN |
| ZIP/Postal code |
37232-6307 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL6429 |
Vanderbuilt University miRNA Bioarray |
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| Samples (6)
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|
| Relations |
| BioProject |
PRJNA108517 |
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