Uncovering new concepts in the treatment of pancreatic cancer

RNA has long been considered an intermediary molecule; DNA swivels and twists into helical delights to curate RNA, which, in turn, codes for protein: also known as the building blocks of life as we know it. From your muscles to the basis of cellular function, without protein, we may as well be blocks of cherry gelatine. 

More recently, scientists have unveiled new findings indicating that of the three billion bases in the human genome, only two per cent encode proteins. The remaining 98 per cent of the genome are non-coding, and once thought to be the 'dark matter' of the human genome, with no known functions. 

Some lncRNAs, a major component of this genomic dark matter, have been shown to play key roles in diverse biological processes, ranging from development to diseases.

The exciting phenomenon here is that by combining several advanced tools, geneticists and other medical specialties are now able to investigate the role and function of 'the dark matter that matters' in pancreatic cancer," so think of this as the black hole on yhe universe... once mysterious and onimous. We now may have a flashlight to delve deeper! 

Specifically, the research team involved in this particulat study seeks to identify lncRNAs that were regulated by a well-known pathway called WNT signalling. What in the world is WNT signalling I hear you ask? 

This pathway regulates many genes that code for proteins, but its influence on lncRNAs has been unclear. This form of signalling was actually first identified for its role in carcinogenesis, then for its function in embryonic development. And now? Protein barrier formation.

Wnt signalling is known to fuel the growth of some pancreatic cancers. Turning off this pathway could not only help treat pancreatic cancer but also help researchers identify the parts of the genome that are regulated by it.

To do this, the research team has turned to a ETC-159, a made-in-Singapore Wnt-suppressing drug jointly developed by Duke-NUS and the Agency for Science, Technology and Research (A*STAR), which is currently progressing through clinical trials as a treatment for a range of cancers, including pancreatic. 

The scientists began to compare what would happen  to lncRNAs when ETC-159 turned off Wnt signalling in preclinical modellings of pancreatic cancers, and in pancreatic cancer cells cultured in the laboratory. 

The investigations lead to a discovery illuminating us on the fact that there was an expression of 1,503 lncRNAs in the former... but only changed the expression of half that number in the latter. This highlights the importance of studying lncRNAs within the context of a more natural environment.

The team then used the gene editing tool CRISPR to study what would happen when the 1,503 Wnt-regulated lncRNAs were turned off in the preclinical model and in pancreatic cell cultures. Twenty-one lncRNAs were found to be able to modify pancreatic cancer cell growth in the living model, whereas only half that number were identified in the cancer cell culture tests.

The takeaway here is that this study provides a unique window in the largely unknown role of the dark matter of the genome that plays a functional role in pancreatic cancer, and will be a valuable resource for the scientific community studying Wnt-regulated lncRNAs in cancer. By beginning to comprehend that a subset of Wnt-regulated lncRNAs can act as mediators of the oncogenic function of Wnt signalling in cancers provides potential new targets for precision cancer therapies 


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©2019 by Lait Mylk