Genomic profiling of DVL-1 and its nuclear role as a transcriptional regulator in triple negative breast cancer
Monica Sharma1, Isabel Castro-Piedras1, Austin Dwight Rodgers1, Kevin Pruitt1
1 Immunology and Molecular Microbiology, Texas Tech University Health Sciences Center, Lubbock, TX, USA
Correspondence:
Kevin Pruitt, email:[email protected]
Keywords: Dishevelled (DVL); ChIP-Seq; transcription; histone modifications; breast cancer
Received: July 07, 2021 Accepted: September 24, 2021 Published: October 13, 2021
Abstract
Dishevelled-1 (DVL-1) mediates Wnt signals critical for development and cellular homeostasis. DVL-1 is also linked with tumorigenesis, howe3ver its association with specific breast cancer (BC) subtypes and how it contributes to tumorigenicity remains poorly studied. Herein, using bioinformatics and genomics analyses, we investigate the role of DVL-1 in different molecular subtypes of BC. Our results demonstrate that DVL-1 is highly expressed in triple-negative BC compared to non-cancer tissues and associated with various clinical factors that may contribute to poor prognosis and survival rate.
Another critical knowledge gap which remains poorly investigated involves the role of DVL-1 in the nucleus. While the cytoplasmic role of DVL-1 as a signaling hub has been extensively studied, the nuclear role of DVL-1 remains virtually unexplored. Herein for the first time, we have performed ChIP-Seq analyses to identify genomic regions targeted and regulated by DVL-1, thus highlighting its potential role as a regulator of transcription. Furthermore, we observed that DVL-1 peaks co-localize with H3K27me3 and EZH2, a repressive epigenetic mark and a histone methyltransferase respectively. Overall, our findings emphasize the importance of DVL-1 with TNBC-related pathology and identified unexpected gene targets of DVL-1, that may help explain the complexity of aberrant Wnt signaling in cancer.
