Mitchell Diccianni's Research on IncRNAs
Research on lncRNAs is a major part of Dr. Diccianni’s current research emphasis. Though long thought to be transcriptional noise and have no functional significance, lncRNAs and are now thought to represent a new paradigm of molecular and transcriptional control. Although the vast majority of these genes are little understood, research now suggests many lncRNAs function to regulate gene expression through chromatin modulation.
The lncRNA CAI2, discovered by Dr. Diccianni, localizes to the intron of one of the most important and widely deregulated tumor suppressor genes in cancer, p16/CDKN2A. Many cancers have deletions of this gene, consistent with its role as a tumor suppressor. Neuroblastoma, paradoxically, overexpresses p16. We hypothesize that this overexpression may be due in part to regulation by CAI2. Notably, CAI2 is regulated independently of p16 and ARF and selectively expressed in tumor cells and associated with a poor prognosis. Current research suggests that like many lncRNAs, CAI2 functions as a modulator of chromatin structure, though this remains under investigation.