Noncoding Transcriptional Landscape in Human Aging

Author(s):  
Marina C. Costa ◽  
Ana Lúcia Leitão ◽  
Francisco J. Enguita
BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Eddie Luidy Imada ◽  
Diego Fernando Sanchez ◽  
Wikum Dinalankara ◽  
Thiago Vidotto ◽  
Ericka M. Ebot ◽  
...  

Abstract Background PTEN is the most frequently lost tumor suppressor in primary prostate cancer (PCa) and its loss is associated with aggressive disease. However, the transcriptional changes associated with PTEN loss in PCa have not been described in detail. In this study, we highlight the transcriptional changes associated with PTEN loss in PCa. Methods Using a meta-analysis approach, we leveraged two large PCa cohorts with experimentally validated PTEN and ERG status by Immunohistochemistry (IHC), to derive a transcriptomic signature of PTEN loss, while also accounting for potential confounders due to ERG rearrangements. This signature was expanded to lncRNAs using the TCGA quantifications from the FC-R2 expression atlas. Results The signatures indicate a strong activation of both innate and adaptive immune systems upon PTEN loss, as well as an expected activation of cell-cycle genes. Moreover, we made use of our recently developed FC-R2 expression atlas to expand this signature to include many non-coding RNAs recently annotated by the FANTOM consortium. Highlighting potential novel lncRNAs associated with PTEN loss and PCa progression. Conclusion We created a PCa specific signature of the transcriptional landscape of PTEN loss that comprises both the coding and an extensive non-coding counterpart, highlighting potential new players in PCa progression. We also show that contrary to what is observed in other cancers, PTEN loss in PCa leads to increased activation of the immune system. These findings can help the development of new biomarkers and help guide therapy choices.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Robin-Lee Troskie ◽  
Yohaann Jafrani ◽  
Tim R. Mercer ◽  
Adam D. Ewing ◽  
Geoffrey J. Faulkner ◽  
...  

AbstractPseudogenes are gene copies presumed to mainly be functionless relics of evolution due to acquired deleterious mutations or transcriptional silencing. Using deep full-length PacBio cDNA sequencing of normal human tissues and cancer cell lines, we identify here hundreds of novel transcribed pseudogenes expressed in tissue-specific patterns. Some pseudogene transcripts have intact open reading frames and are translated in cultured cells, representing unannotated protein-coding genes. To assess the biological impact of noncoding pseudogenes, we CRISPR-Cas9 delete the nucleus-enriched pseudogene PDCL3P4 and observe hundreds of perturbed genes. This study highlights pseudogenes as a complex and dynamic component of the human transcriptional landscape.


Aging Cell ◽  
2009 ◽  
Vol 8 (3) ◽  
pp. 339-342 ◽  
Author(s):  
Bin Tang ◽  
Wei-li Chang ◽  
Caroline M. Lanigan ◽  
Brian Dean ◽  
J. Gregor Sutcliffe ◽  
...  

Nature Aging ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 101-113
Author(s):  
Emma S. Chambers ◽  
Milica Vukmanovic-Stejic ◽  
Barbara B. Shih ◽  
Hugh Trahair ◽  
Priya Subramanian ◽  
...  

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