Oncogenic LINE 1 Retroelements Sustain Prostate Tumor Cells and Promote Metastatic Progression
Technical Report,30 Sep 2014,29 Sep 2015
University of Texas San Antonio United States
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The goal of this hypothesis development project was to determine if expression of LINE-1 elements in prostate tumor metastases contribute to its progression by activating oncogenic DNA sequences, or silencing tumor suppressor like sequences. We have RNA-sequencing data that we developed novel pipelines to analyze what is typically called junk sequence and removed from standard RNA-seq analysis pipelines, and have developed a database of novel sequences that are expressed in lymph node metastases from prostate cancer, and contain a portion of LINE-1 element, in addition to a portion of another transcript. Interestingly, the standard analysis pipeline suggests significant activation of non-coding RNA sequences as well. Furthermore, we cloned a repressor of LINE-1 retroelements, the PIWIL1 gene, it put it under the control of a doxycycline-inducible promoter. Expression of this in LNCaP and PC-3 prostate cancer cells was robust, but had no effect on the cells as long as three single-nucleotide variations were present. When wild-type PIWIL1 was expressed induction was nearly impossible suggesting that the agonaute interacting domain is critical to the function of this protein and cells expressing it can not live, potentially providing proof-of-principle for future gene-based therapeutics for this cancer.
- Medicine and Medical Research