Researchers have harnessed the power of CRISPR gene-editing technology to uncover a key gene that could revolutionize cancer treatment by targeting vitamin D metabolism. Published in Frontiers in Endocrinology, the research reveals that the gene SDR42E1 plays a critical role in how the body absorbs and processes vitamin D, transforming it into calcitriol, a hormone vital for bone health, immune function, and cell growth.

By disabling this gene in colorectal cancer cells, scientists found they could halt tumor growth, offering a promising new avenue for precision medicine. The research team used CRISPR/Cas9 to deactivate SDR42E1 in HCT116 colorectal cancer cells, which typically rely on high levels of this gene to survive.
The results were striking: cancer cell viability plummeted by 53%, and the expression of 4,663 downstream genes—many linked to cancer signaling and cholesterol-like molecule metabolism—was disrupted. This suggests SDR42E1 acts as a molecular switch, controlling pathways essential for cancer cell survival. Crucially, the approach selectively targeted cancer cells without harming neighboring healthy ones, a key advantage for developing therapies with fewer side effects. The findings build on earlier research linking a mutation in SDR42E1, located on chromosome 16, to vitamin D deficiency. This mutation produces an inactive, truncated protein, hinting at the gene’s importance. By mimicking this fault in cancer cells, the team effectively starved them of vitamin D’s benefits, crippling their growth.

Enhancing SDR42E1 activity could boost calcitriol levels, potentially benefiting conditions like kidney disease, autoimmune disorders, or even cancer prevention, where vitamin D plays a regulatory role. However,  there is need for caution, as altering vitamin D metabolism could have unforeseen consequences. The complexity of SDR42E1’s influence, affecting thousands of genes, underscores the challenge of translating these findings into safe, effective treatments.

This discovery marks a significant step forward in understanding vitamin D’s role in health and disease. By leveraging CRISPR’s precision, the researchers have opened the door to therapies that could either starve tumors of vital nutrients or enhance vitamin D’s protective effects.

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