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| Status |
Public on Jan 17, 2017 |
| Title |
Modulation of microRNA-mRNA Target Pairs by Human Papillomavirus 16 Oncoproteins |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Non-coding RNA profiling by high throughput sequencing
|
| Summary |
The E6 and E7 proteins are the major oncogenic drivers encoded by high-risk human papillomaviruses (HPVs). While many aspects of the transforming activities of these proteins have been extensively studied, there are fewer studies that have investigated how HPV E6/E7 expression affects expression of cellular noncoding RNAs. The goal of our study was to investigate HPV16 E6/E7 modulation of cellular microRNA (miR) levels and to determine the potential consequences on cellular gene expression. We performed deep sequencing of small and large cellular RNAs in primary, undifferentiated cultures of human foreskin keratinocytes (HFKs) with stable expression of HPV16 E6/E7 or a control vector. After integration of the two data sets we identified 51 differentially expressed cellular miRs associated with modulation of 1,456 potential target mRNAs in HPV16 E6/E7 expressing HFKs. We discovered that the degree of differential miR expression in HFKs expressing HPV16 E6/E7 was not necessarily predictive of the number of corresponding mRNA targets or the potential impact on gene expression. Additional analyses of the identified miR-mRNA pairs suggest modulation of specific biological activities and biochemical pathways. Overall, our study supports the model that perturbation of cellular miR expression by HPV16 E6/E7 importantly contributes to the rewiring of cellular regulatory circuits by the high-risk HPV E6 and E7 proteins that contribute to oncogenic transformation.
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| Overall design |
A total of 8 samples were analyzed, including two replicates of donor and passage matched human foreskin keratinocyte populations transduced with a control LXSN vector, a vector expressing HPV16 E6 alone, HPV16 E7 alone or both HPV16E6 and E7. Large and smal RNA was harvested from each of these samples. RNAseq was performed using large RNA from two populations expressing a control vector and two populations expressing HPV16 E6 and E7 together only (a total of 4 samples). All 8 samples were subjected to small RNAseq (miRNAseq).
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| Contributor(s) |
Harden ME, Prasad N, Griffiths A, Munger K |
| Citation(s) |
28049151 |
| Submission date |
Dec 16, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Nripesh Prasad |
| E-mail(s) |
nprasad@hudsonalpha.org
|
| Phone |
2562261750
|
| Organization name |
Hudson Alpha Institute for Biotechnology
|
| Street address |
601 Genome way
|
| City |
Huntsville |
| State/province |
Alabama |
| ZIP/Postal code |
35806 |
| Country |
USA |
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| Platforms (2) |
| GPL15520 |
Illumina MiSeq (Homo sapiens) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA357712 |
| SRA |
SRP095254 |
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