Vitamin D regulation of and by long non coding RNAs.

Two percent or less of the genome is used to transcribe mRNAs encoding proteins. Nearly all the remainder is utilized in transcribing non coding RNAs, the bulk of which are RNAs at least 200 base in length, long non coding RNAs (lncRNA). Their number is estimated to be about 28,000, but only a small fraction of lncRNAs are well characterized. That said lncRNAs have been found to regulate a very diverse array of biochemical and genomic functions. One of the transcription factors found to be regulated by and to regulate lncRNA is the vitamin D receptor (VDR). Like lncRNAs VDR is involved in the regulation of numerous biochemical and genomic processes, so it is not surprising that there would be a number of interactions between lncRNAs and VDR in their diverse functions. However, the study of these interactions is in its infancy. To date most attention has been paid to their interactions in cancer. Our own studies have focused on non melanoma skin cancers, keratinocyte carcinomas to be precise. Deletion of VDR from keratinocytes predisposes them to malignant transformation. Among a number of potential mechanisms we found that VDR deletion from these cells alters the lncRNA profile to a more oncogenic configuration, increasing the expression of well known oncogenic lncRNAs and decreasing the expression of well known tumor suppressor lncRNAs. Subsequent studies in other cancers have found similar associations between VDR and oncogenic lncRNAs with evidence of tumor specificity. To date these studies primarily reveal associations rather than causality, but causal links should be expected as research in this field continues to develop.