Gene That Turns Sunshine into Cancer Killer

This gene helps the body absorb vitamin D—which is important for bones, muscles, and immunity—but researchers discovered it also plays a powerful role in cancer. When they switched the gene off in cancer cells, the tumors stopped growing. This breakthrough could lead to new treatments that either block the gene to fight cancer or boost it to improve health in other conditions like autoimmune diseases, the journal Frontiers in Endocrinology reported.

Vitamin D is widely known as a vital nutrient, but it also plays another critical role. It serves as the building block for calcitriol, a hormone that helps the body absorb calcium and phosphate—minerals that are essential for strong bones. Calcitriol also supports healthy muscle and nerve function, regulates cell growth, and plays a crucial role in maintaining the proper functioning of the immune system.

In a new stud, scientists have identified a gene called SDR42E1 as essential for how the body absorbs vitamin D through the digestive system and processes it further. This finding could have major implications for targeted treatments, especially in areas like cancer care.

“Here we show that blocking or inhibiting SDR42E1 may selectively stop the growth of cancer cells,” said Dr. Georges Nemer, a professor and associate dean for research at the University of College of Health and Life Sciences at Hamad Bin Khalifa University in Qatar, and the study’s corresponding author.

The research team was motivated by previous studies that linked a specific mutation in the SDR42E1 gene, located on chromosome 16, with vitamin D deficiency. This mutation shortened the gene’s protein product, rendering it inactive.

To explore its role further, the team used CRISPR/Cas9 gene-editing technology to deactivate SDR42E1 in a colorectal cancer cell line known as HCT116. These cells typically exhibit high levels of SDR42E1, suggesting that the gene may be crucial for their survival. Once the gene was inactivated, the cancer cells were no longer able to thrive.

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.

“Our results open new potential avenues in precision oncology, though clinical translation still requires considerable validation and long-term development,” said Dr. Nagham Nafiz Hendi, a professor at Middle East University in Amman, Jordan, and the study’s first author.

But starving selected cells of vitamin D is not the only possible application that immediately sprang to the mind of the researchers. 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.

“Because SDR42E1 is involved in vitamin D metabolism, we could also target it in any of the many diseases where vitamin D plays a regulatory role,” said Nemer.

“For example, nutrition studies have indicated that the hormone can lower the risk of cancer, kidney disease, and autoimmune and metabolic disorders.”

“But such broader applications must be done with caution, as long-term effects of SDR42E1 on vitamin D balance remain to be fully understood,” warned Hendi.

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