Inhibition of RNA Binding in SND1 Increases the Levels of miR-1-3p and Sensitizes Cancer Cells to Navitoclax.

ABSTRACT: SND1 is an RNA-binding protein overexpressed in large variety of cancers. SND1 has been proposed to enhance stress tolerance in cancer cells, but the molecular mechanisms are still poorly understood. We analyzed the expression of 372 miRNAs in the colon carcinoma cell line and show that SND1 silencing increases the expression levels of several tumor suppressor miRNAs. Furthermore, SND1 knockdown showed synergetic effects with cancer drugs through MEK-ERK and Bcl-2 family-related apoptotic pathways. To explore whether the SND1-mediated RNA binding/degradation is responsible for the observed effect, we developed a screening assay to identify small molecules that inhibit the RNA-binding function of SND1. The screen identified P2X purinoreceptor antagonists as the most potent inhibitors. Valid

SUBMITTER: Lehmusvaara S 

PROVIDER: S-EPMC9265050 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature