University of Bath and University of Cambridge researchers have discovered that a specific noncoding RNA strand, originating from “junk” DNA, prevents the overgrowth of cells that can lead to cancer and tumor metastasis. Importantly, the genomic region where this noncoding RNA is located is often damaged in breast cancer patients. The paper, “Transcriptional silencing of long noncoding RNA GNG12-AS1 uncouples its transcriptional and product-related functions,” was published in Nature Communications.
“Junk” DNA is a term used to describe about 98 percent of the human genome that does not code for functional proteins. This noncoding DNA is transcribed into noncoding RNA, which previous research has shown is involved in gene regulation during disease development and pathogenesis. However, the exact mechanisms by which noncoding RNAs regulate gene expression are not quite understood. To further investigate, researchers used small interference RNA (siRNA) to study the action of a noncoding RNA strand, GNG12-AS1, on the tumor-suppressor DIRAS3 gene. DIRAS3 is downregulated in 70 percent of breast and ovarian cancers, and its loss of expression is correlated to cancer progression and metastasis.
Using siRNAs to either prevent noncoding RNA formation or degrade it after production, researchers found that GNG12-AS1 prevented the excessive cell growth which can sometimes lead to cancer, and it suppressed metastasis, the process by which tumor cells travel through the bloodstream to other parts of the body. The team also found that GNG12-AS1 maintains the health of cells through two distinct mechanisms: by regulating the levels of DIRAS3 and by suppressing a network of genes involved in cell shape modifications and the initiation of metastasis.
“Only a tiny fraction of our DNA contains actual genes, and we know that at least some of the bits in between — often dismissed as ‘junk’ — play important roles in controlling how genes get switched on and off at the right time and in the right place,” Dr. Kat Arney, science communication manager at Cancer Research UK, the institute that funded the study, said in a press release. “Research like this is helping [us] to unpick the precise details about how these regions work, shedding light on their potential role in the development of cancer and pointing towards new approaches for tackling the disease.”