<i>SCIRT</i> lncRNA Blocks the Shot of Breast Cancer Cells Self-Renewal Mechanism.

Abstract

The study by Zagorac and colleagues represents an important step forward in the field of breast cancer, explaining a novel molecular mechanism of transition from slowly multiplying tumor-initiating cells (TIC) into their more differentiated version characterized by high proliferation. The mechanism involves the transcription factors SOX2 and EZH2, which directly repress transcription of cell-cycle genes and activate self-renewal genes in breast cancer cells. This mechanism is further controlled by a negative feedback loop mediated by a long noncoding RNA, <i>SCIRT</i>, not described previously, which is upregulated in tumorspheres and inhibits SOX2 and EZH2. <i>SCIRT</i> is an atypical tumor suppressor in breast cancer, being upregulated in cancer cells, but counteracting their aggressive phenotype. At the molecular level, by direct interaction with EZH2, <i>SCIRT</i> inhibits the transcriptional activity of EZH2 and "blocks the shot" of cancer cells' self-renewal. From a translational perspective, activating <i>SCIRT</i> or induction of SCIRT mimetics in breast cancer cells may lead to the dedifferentiation of TICs toward a less protumorigenic phenotype and a therapy-fragile state that could open new therapeutic avenues.<i>See related article by Zagorac et al., p. 580</i>.