LINC01432 binds to CELF2 in newly diagnosed multiple myeloma promoting short progression-free survival to standard therapy

Abstract Multiple Myeloma (MM) is an incurable form of cancer that arises from malignant plasma cells, with over 35,000 new cases diagnosed annually in the United States. While there are a growing number of approved therapies, MM remains incurable and nearly all patients will relapse and exhaust available treatments. Mechanisms for disease progression are unclear and little is known regarding the role of long non-coding RNAs (lncRNA) in mediating disease progression and response to treatment. Here, we used transcriptome sequencing to compare newly diagnosed MM (NDMM) patients who had short progression-free survival (PFS) to standard first-line treatment (PFS 24 months). We identified 157 differentially upregulated lncRNAs with short PFS and focused our efforts on characterizing the most upregulated lncRNA, LINC01432. We investigated LINC01432 to show that its overexpression significantly increases cell viability and reduces apoptosis, while knockdown significantly reduces viability and increases apoptosis. Next, we show that LINC01432 directly interacts with the RNA binding protein, CELF2. Lastly, we showed that LINC01432-targeted locked nucleic acid antisense oligonucleotides reduce viability and increases apoptosis. In summary, this fundamental study identified lncRNAs associated with short PFS to standard NDMM treatment and further characterized LINC01432.