Science Advances: 'Junk DNA' May Hold the Key to New Cancer Treatments

Researchers from Arizona State University, together with an international team of scientists, have found that so-called "junk DNA" may play a critical role in regulating cellular processes involved in cancer development and could provide the foundation for new cancer therapies. The study was published in Science Advances.

The research focused on long non-coding RNAs (lncRNAs)—segments of the genome that do not encode proteins but help regulate gene activity. Once considered nonfunctional "junk," these molecules are now recognized as important regulators of cellular behavior and have been implicated in a wide range of diseases, including cancer.

As part of the study, the researchers performed a comparative genomic analysis of approximately 18,000 lncRNAs across 17 animal species, tracing their evolutionary history over nearly 500 million years. Around 5,000 of these molecules were found to be associated with various forms of cancer and were selected for further investigation.

The team discovered that many lncRNAs originated as small fragments of genetic material before gradually increasing in length and becoming integrated into ancient cellular regulatory networks that evolved hundreds of millions of years ago.

One molecule, MIR497HG, received particular attention. According to the study, it likely originated in the common ancestor of humans and other primates around 29 million years ago as a microRNA before evolving into a more complex regulatory RNA that became integrated into ancient signaling pathways involved in metabolism, cellular stress responses, and programmed cell death.

Experiments using cancer cell models showed that reducing MIR497HG expression promoted tumor cell growth, whereas restoring its expression suppressed cancer cell proliferation, suggesting that the molecule may have significant therapeutic potential.

The researchers also identified links between MIR497HG, the AMPK signaling pathway, and ferroptosis—a form of programmed cell death driven by iron-dependent lipid damage. They propose that disruption of this regulatory network may contribute to tumor development while also revealing promising new therapeutic targets.

According to the authors, these relatively "young" regulatory RNAs gradually become incorporated into ancient biological networks, increasing the complexity of genetic regulation but also making these systems more vulnerable to dysfunction, including cancer.

The findings also support the neutral theory of evolution, which suggests that newly emerged genetic elements may persist for long periods without a clear biological function before eventually being integrated into existing regulatory systems.

The researchers conclude that further investigation of lncRNAs could open new opportunities for cancer diagnosis and treatment, including their use as biomarkers and therapeutic targets.