Coding and noncoding genes are involved in and cooperate in human tumorigenesis

A new study provides evidence that noncoding RNAs and interactions between noncoding genes play a much greater role in human cancer than was previously understood.

The research, published by Cell Press in the September issue of the journal Cancer Cell, may be useful for identifying tumor-specific signatures associated with diagnosis, prognosis, and treatment of cancer.

Malignant cells exhibit genetic alterations in oncogenes or tumor suppressor genes. More recently, a large class of noncoding RNA transcripts called microRNAs (miRNAs) has also been included in the genetic signature of cancer. MicroRNAs are small RNAs that can regulate gene expression by inhibiting protein translation, and recent research has implicated miRNAs in cancer initiation and progression.

Dr. Carlo M. Croce from Ohio State University, Dr. Massimo Negrini from the University of Ferrara, Italy, and colleagues investigated the role of additional classes of highly conserved noncoding RNAs in human cancer that have not been studied to the extent of miRNAs. “This research will offer new insights into the molecular mechanisms and signal transduction pathways altered in cancer and may present opportunities for the identification of new molecular markers and potential therapeutic agents,” explains Dr. Croce.

Using genome-wide profiling in a large panel of normal and cancer samples, the researchers discovered that genomic ultraconserved regions (UCRs) encode a particular set of noncoding RNAs whose expression is altered in human leukemias and carcinomas. These UCRs are highly conserved among different species, and although they do not encode proteins, they are likely to be functional. Inhibition of an overexpressed UCR induced apoptosis in colon cancer cells. Interestingly, the researchers also identified a functional role of miRNAs in the transcriptional regulation of UCRs associated with cancer.

Taken together with the current knowledge of miRNAs, these results provide strong support for a model that considers alteration of both coding and noncoding RNAs in the initiation and progression of human cancer. “We found that noncoding UCRs are consistently altered at the genomic level in a high percentage of leukemias and carcinomas and may interact with miRNAs. The findings provide support for a model in which both coding and noncoding genes are involved in and cooperate in human tumorigenesis,” concludes Dr. Croce. Further research is needed to investigate the complex functional interactions between multiple types of noncoding RNAs.

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