Genome-wide feature analysis of the sequence-specific recognition in intermolecular interaction between TGF- pathway DNA and MEG3 lncRNA in human cancer

The long noncoding RNAs MEG3 is involved in the pathogenesis and metastasis of cancer, which has been found to target the distal regulatory elements (DREs) of TGF- pathway genes TGFBR1, TGFB2, and SMAD2 by forming DNA-RNA triplex. Here, the molecular mechanism of MEG3 binding to its cognate or noncognate DNA partners is investigated systematically via an integrative chemometric approach. Here, we apply a spatial information characterization technique to capture the structural and energetic features of DNA-RNA triplex architecture and then to correlate the extracted features with binding potency of the triplex complexes. A genome-wide statistical analysis strategy is used to quantitatively evaluate the intermolecular interaction between DNA with RNA in a high-throughput manner. The strategy is then employed to examine the binding potency and recognition specificity of MEG3 with its interacting DRE partners TGFBR1, TGFB2, and SMAD2. As might be expected, the abundance of GA nucleotide residues in DNA core motif exhibits a positive correlation with the affinity of MEG3 binding to the DREs of TGF- pathway, while the MEG3 possesses a moderate specificity for its known cognate DNA partners on the background of numerous random decoys. Therefore, it is suggested that the MEG3 has a broad spectrum of potential targets in the human genome and may regulate diverse cell biological events. The sequence-specific recognition in intermolecular interaction between cancer MEG3 lncRNA and its cognate or noncognate TGF- pathway DNA is investigated in a genome-wide background via an integrative chemometric approach. It is revealed that the GA abundance of DNA exhibits a positive correlation with the affinity of MEG3 binding to TGF- genes and the MEG3 possesses a moderate specificity for its cognate DNA partners.