Crispr instruments. Image by Tim Sandle (taken at the Design Museum, London).
Scientists are hailing a key gene, said to present promising ‘new avenues’ for precision medicine through CRISPR/Cas9, with a probable application directed towards tumours.
Through the research, a gene called SDR42E1 has been identified as a key player in how our bodies absorb and process vitamin D. Researchers have found that disabling this gene in colorectal cancer cells not only crippled their survival but also disrupted thousands of other genes tied to cancer and metabolism.
This finding, from University of College of Health and Life Sciences at Hamad Bin Khalifa University in Qatar, opens the door to highly targeted cancer therapies—by either cutting off vitamin D supply to tumors or enhancing the gene’s activity to boost health. The findings hint at vast possibilities in treating diseases influenced by vitamin D, though long-term impacts remain uncertain.
Specifically, vitamin D is an essential nutrient; it is also the precursor of the hormone calcitriol, indispensable for health: it regulates the uptake of phosphate and calcium necessary for bones by the intestines, as well as cell growth and the proper function of muscles, nerve cells, and the immune system.
The scientists have identified how a particular gene, called SDR42E1, is crucial for taking up vitamin D from the gut and further metabolizing it – a discovery with many possible applications in precision medicine, including cancer therapy.
The researchers used CRISPR/Cas9 gene editing to transform the active form of SDR42E1 in a line of cells from a patient with colorectal cancer, called HCT116, into its inactive form. In HCT116 cells, the expression of SDR42E1 is usually abundant, suggesting that the protein is essential for their survival.
Once the faulty SDR42E1 copy had been introduced, the viability of the cancer cells plummeted by 53%. No fewer than 4,663 ‘downstream’ genes changed their expression levels, suggesting that SDR42E1 is a crucial molecular switch in many reactions necessary for the health of cells. Many of these genes are normally involved in cancer-related cell signaling and the absorption and metabolism of cholesterol-like molecules – consistent with the central role of SDR42E1 in calcitriol synthesis.
These results suggest that inhibiting the gene can selectively kill cancer cells, while leaving neighboring cells unharmed. The present results suggest that SDR42E1 cuts two ways: artificially ‘dialing up’ levels of SDR42E1 in local tissues through gene technology might likewise be beneficial, leveraging the many known health effects of calcitriol.
The research appears in the journal Frontiers, titled “CRISPR uncovers gene that supercharges vitamin D—and stops tumors in their tracks.”