Selective Small-Molecule Targeting of a Triple Helix Encoded by the Long Noncoding RNA, MALAT1.

ABSTRACT: Metastasis-associated lung adenocarcinoma transcript 1 ( Malat1/ MALAT1, mouse/human), a highly conserved long noncoding (lnc) RNA, has been linked with several physiological processes, including the alternative splicing, nuclear organization, and epigenetic modulation of gene expression. MALAT1 has also been implicated in metastasis and tumor proliferation in multiple cancer types. The 3' terminal stability element for nuclear expression (ENE) assumes a triple-helical configuration that promotes its nuclear accumulation and persistent function. Utilizing a novel small molecule microarray strategy, we identified multiple Malat1 ENE triplex-binding chemotypes, among which compounds 5 and 16 reduced Malat1 RNA levels and branching morphogenesis in a mammary tumor organoid model. Computationa

SUBMITTER: Abulwerdi FA 

PROVIDER: S-EPMC6709583 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature