Novel Small Molecule Antagonists Targeting Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1) Long Non-coding RNA (lncRNA) as Anticancer Agents

Human metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA) overexpressed in multiple human cancers. There is a strong correlation between MALAT1 levels and increased risk of various malignancies including metastasis. Antisense oligonucleotide inhibition of MALAT1 expression levels has shown promising anticancer effects in vivo. Additionally, depletion of MALAT1 is not lethal to normal cell growth, further supporting MALAT1 as a promising therapeutic target for cancer therapy.The enhancement of oncogenic processes by MALAT1 in cancers has been localized to its 3 ’-end sequence.  The structure of this region is suggested to contribute to RNA stability, and that triple helix formation blocks exonucleolytic RNA degradation. MALAT1 3’-end triple helix formation was confirmed with a recent crystal structure showing the 3’-end A-rich region engaged in a tr iple helix with nuclear retention element (ENE). Development of small molecules that recognize and disrupt MALAT1 triple helix structure (designated MALAT1 ENE), and ultimately its degradation, would provide novel therapeutics for cancers associated with enhanced levels of MALAT1.Researchers at the National Cancer Institute (NCI) have developed an invention describing the identification of MALAT1 ENE binding ligands. The ligands have been further studied for their ability for reverse branching morphogenesis in tumor-derived organoids. The inventors have demonstrated a ~50% drop i...
Source: NIH OTT Licensing Opportunities - Category: Research Authors: Source Type: research