Doha – The Qatar Biomedical Research Institute (QBRI), part of Hamad Bin Khalifa University (HBKU), recently published articles in two prestigious scientific journals identifying research findings on gene regulation in human cancers and a new method of classifying tumors that may lead to a tailored treatment for triple-negative breast cancer.
One of the most startling findings from recent genomics research is that only 2% of the human genome codes for functional proteins, an essential component of the work done by living cells. The function of the vast majority of the remaining genome – the so-called “dark matter” or “junk DNA” – remains to be elucidated. These data are surprising, given that approximately 75% of the genome may be active in a cell at any time.
“Emerging findings have revealed the transcription (or copying) of the vast majority of our DNA into RNA, without it being translated into functional proteins (called non-coding RNAs). However, having worked in the field of non-coding RNAs for more than 15 years, we know more than ever about their regulatory role in different cellular functions and their importance in tumor formation (tumorigenesis),” explained Dr. Nehad. Alajez, principal investigator at the Translational Center for Cancer and Immunity (TCIC) at QBRI.
In an article published in the prestigious Seminars in Cancer Biology by Elsevier, Dr. Alajez and his team highlight the crucial role of long non-coding RNAs (ncRNAs) in the regulation of the genome via their interactions with RNA-binding proteins (RBPs). The article covers various aspects of the interaction between lncRNAs and RBPs in the context of human cancers.
In breast cancer, a major problem accounting for the majority of cancer-related deaths in women, is the heterogeneous nature of the disease. While the classification of breast cancer into three types, HR-positive, HER2-positive and triple-negative (TNBC) breast cancer, has made it possible to propose a treatment adapted to patients of each subtype, tumor heterogeneity (variations in types of cancer cells within the same tumor) and differences in how patients respond to treatment remain a major clinical challenge.
Thinking differently is key to success, according to Dr. Alajez, who brings strong expertise in transcriptome analysis, non-coding RNAs and biomarker discovery to QBRI’s TCIC in their current focus on translational oncology and research. in precision medicine. In a second article, published in non-coding RNA, an open-access MDPI journal, the team used a novel approach to characterize the expression of tens of thousands of ncRNAs in TNBC, using artificial intelligence (AI) to unravel disease heterogeneity. The team was able to categorize TNBC into four different groups, with each group expressing a defined set of lncRNAs.
The authors revealed functional differences between the identified clusters and predicted the relapse-free survival of patients based on this new classification method. These results could potentially impact the stratification of patients into subgroups within the TNBC subtype, for personalized treatment in the future.
To develop this area, the team is currently conducting a large-scale experiment, using a gene editing tool (called CRISPR-Cas9 screening) that allows the manipulation of DNA in the cell to study their function. The results will offer insight into the function of hundreds of ncRNAs in TNBC, paving the way for the use of these candidates as potential prognostic and therapeutic targets. The results may provide the first-ever lncRNA dependency map of TNBC in the context of chemotherapy resistance. The research is carried out in collaboration with University College Dublin, with support from the Qatar National Research Fund.
For more information about QBRI’s Translational Cancer and Immunity Center, a national center of excellence and global center for biomedical and translational research related to diabetes, cancer and neurological disorders, please visit qbri.hbku.edu.qa .
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About Hamad Bin Khalifa University
Innovate today, shape tomorrow. Hamad Bin Khalifa University (HBKU), a member of the Qatar Foundation for Education, Science and Community Development (QF), was founded in 2010 as a research-intensive university that acts as a catalyst of transformative change in Qatar and the region while having global impact. Located in Education City, HBKU is committed to strengthening and cultivating human capabilities through an enriching academic experience, an innovative ecosystem, and unique partnerships. HBKU offers multidisciplinary undergraduate and graduate programs in its colleges and offers research and scholarship opportunities in its institutes and centers. For more information about HBKU, visit www.hbku.edu.qa.