Decoding of Non-Coding DNA and Non-Coding RNA: Pri-Micro RNA-Encoded Novel Peptides Regulate Migration of Cancer Cells
Only two percent of the Human genome was shown to code for proteins and the rest of the 80–90 percent was shown to transcribe into non-coding RNAs. Micro RNAs (miRNAs) and long non coding RNAs (lncRNAs) fall into this category of non-coding RNAs. miRNAs are regulatory small RNA molecules that base pair with 3-prime-untranslated region of mRNAs and inhibit the translation or expression of mRNA. Mature miRNAs are known to be processed from large primary transcript (pri-miRNAs) in two stages. First stage involves processing of pri-miRNA into shorter pre-miRNA followed by second stage, where pre-miRNA will be processed to mature miRNAs. Earlier studies suggested that deregulation or aberrant expression of miRNAs can lead to several human diseases and cancers. Recently, it was shown that pri-miRNA codes for peptides (miPEPs) that regulate the expression of active mature miRNAs in plant cells. Since miRNAs are well conserved in humans, animals and plants, it is important to study whether pri-miRNAs code for such peptides/proteins in mammalian cells. In addition, it will be highly significant and remarkable, if one can prove the presence/absence of pri-miRNA encoded peptides in normal and cancer cells and their metastatic cells and show that they function as tumor suppressors and/or oncogenes like in the case of miRNAs. Here, we demonstrate for the first time, the presence of an ORF in pri-miRNA which codes for—peptides or small proteins that show novel biological properties in human cells. We show these pri-miRNA (miR-200a and miR-200b)-encoded peptides/proteins (miPEP-200a and miPEP-200b) to inhibit the migration of prostate cancer cells by regulating epithelial to mesenchymal transition of these cells. These miPEPs have the potential to serve as diagnostic markers for metastasis and can also be used as therapeutic agents to many cancers. We have also discussed how these novel peptides/proteins encoded by pri-miRNAs are evolved in nature and their potential role in cancer and other human diseases. These results may revolutionize our present understanding of the functional role of the so called junk DNA (non-coding DNA) and its noncoding RNAs in the biology of humans and animals.
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Document Type: Research Article
Publication date: March 1, 2017
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