The long non-coding RNA CRNDE stabilises SIRT1 protein and influences Hedgehog signalling in multiple myeloma

Abstract

Multiple myeloma (MM) is a malignancy of immunoglobulin-secreting plasma cells that represents 10% of all hematological cancers and remains essentially incurable, despite recent advances. Long non-coding RNAs (lncRNAs) are an important class of regulatory molecules that have been strongly implicated in the aetiology of MM. Colorectal Neoplasia Differentially Expressed (CRNDE) is one lncRNA that is upregulated in tumor plasma cells of MM patients and contributes to disease progression and outcome. In order to characterise the molecular mechanisms of CRNDE action in MM, here we have carried out a high-throughput screen to identify proteins interacting with this lncRNA inside cells. From the output of this screen, we demonstrate that in MM cells, CRNDE interacts with and stabilises the deacetylase protein SIRT1, previously identified as an important mediator of the Hedgehog (Hh) signalling pathway in MM. We further show that CRNDE exerts downstream effects on MM cell survival, tumorigenic potential, and stem-like properties via an effect on the SIRT1/Hh signalling axis. Our findings add to the molecular understanding of the pro-tumorigenic activity of CRNDE in MM and could have wider implications in other malignant diseases.