The University of Texas MD Anderson Cancer Center recently announced that a collaborative study involving MD Anderson researchers discovered that a specific RNA molecule is capable of regulating cancer metabolism both in vitro and in vivo. The finding was presented on April 20 in Philadelphia at the 2015 American Association for Cancer Research (AACR) Annual Meeting.
Long non-coding RNAs (lncRNA) are a diverse class of RNA molecules with a length of more than 200 nucleotides that do not encode proteins. LncRNAs are thought to play an important role in regulating cellular functions. Researchers have now discovered that an lcnRNA known as CCAT2 (colon cancer associated transcript 2) is able to regulate cancer metabolism. It has been previously shown that CCAT2 is located in a DNA sequence associated to an increased risk of colon cancer and that it is highly expressed in colorectal cancer, promoting tumor growth and spread (metastasis).
“Altered energy metabolism is a cancer hallmark as malignant cells tailor their metabolic pathways to meet their energy requirements,” explained Dr. George Calin from MD Anderson in a news release.
Given the altered energy metabolism observed in cancer, the research team analyzed two of the main nutrients supporting cellular metabolism, the amino acid glutamine and the sugar glucose. “The pathways that use these nutrients are often changed in cancer,” noted Dr. Roxana Redis from MD Anderson.
Researchers found that lcnRNA CCAT2 binds to the cleavage factor I (CFIm) complex, and that this RNA:protein complex (CCAT2:CFIm) regulates the metabolic enzyme glutaminase 1 (GLS1), leading to a preferential expression of the more catalytically active GLS1 isoform that results in feeding of the accelerated growth and proliferation of cancer cells. “While we are not saying that an increased risk for cancer results from this interaction, it may contribute to it,” said Dr. Calin. “More studies are needed to learn more about this new development. In our study, we found that CCAT2 regulated cancer metabolism (…). This study was novel in that it uncovered complex mechanisms of cancer metabolism and regulation controlled by a long non-coding RNA,” concluded Dr. Calin. The results reported were found both in vitro in human colorectal cancer samples and in vivo with animal models.
