MicroRNA-10b (miR-10b) is a regulatory molecule that is silenced in normal cells of the brain but becomes abundant in more than 90 percent of high-grade gliomas.

Glioblastomas (GBM) — the highest grade of glioma — appear to be addicted to this microRNA: without it, cancer cells die.

In a new study, the investigators examined derepression of miR-10b to uncover the mechanism by which the microRNA gets turned back on in GBM.

The researchers found that miR-10b as well as several HOXD genes were commonly activated in gliomas, despite a lack of locus amplification or common mutations.

The team performed a detailed epigenetic analysis of normal and cancer cells and tissues and found a new mechanism that involves topologic reorganization of chromatin and implicates two long-non-coding RNAs.

One of these molecules, an enhancer RNA, was sufficient to turn miR-10b and multiple HOXD genes back on to promote cancer growth; inactivating the molecule in glioma cells reduced glioma viability.

“Our work provides new insights into the question of glioma origin,” said corresponding author. “Our study identifies a new regulatory layer that may drive the genesis of high-grade gliomas, implies the unique vulnerability of tumor-initiating cells and points to new RNA- targeted strategies for glioma therapy.”

https://www.cell.com/molecular-cell/fulltext/S1097-2765(22)00256-8