Research
Print page Print page
Switch language
Rigshospitalet - a part of Copenhagen University Hospital
Published

Genome-Wide Circular RNA Expression Patterns Reflect Resistance to Immunomodulatory Drugs in Multiple Myeloma Cells

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Possible Relevance of Soluble Luteinizing Hormone Receptor during Development and Adulthood in Boys and Men

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Changes in the Tumor Immune Microenvironment during Disease Progression in Patients with Ovarian Cancer

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Optimal Systemic Treatment of Advanced Bladder Cancer-A Moving Target

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Larotrectinib versus Prior Therapies in Tropomyosin Receptor Kinase Fusion Cancer: An Intra-Patient Comparative Analysis

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Protein phosphatase, Mg2+/Mn2+-dependent 1D (PPM1D) mutations in haematological cancer

    Research output: Contribution to journalReviewpeer-review

  2. Detailed Long-Term Follow-Up of Patients Who Relapsed After the Nordic Mantle Cell Lymphoma Trials: MCL2 and MCL3

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. The Thioredoxin-Interacting Protein TXNIP Is a Putative Tumour Suppressor in Cutaneous T-Cell Lymphoma

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Clinical impact of clonal hematopoiesis in patients with lymphoma undergoing ASCT: a national population-based cohort study

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

Immunomodulatory drugs (IMiDs), such as lenalidomide and pomalidomide, may induce significant remissions in multiple myeloma (MM) patients, but relapses are frequently observed and the underlying molecular mechanisms for this are not completely understood. Circular RNAs (circRNAs) constitute an emerging class of non-coding RNAs with important roles in cancer. Here, we profiled genome-wide expression patterns of circRNAs in IMiD-sensitive MM cells and their resistant counterparts as well as in IMiD-resistant cells treated with specific epigenetic drugs alone or in combination. We found that genome-wide circRNA expression patterns reflect IMiD sensitivity and ciRS-7 (also known as CDR1as) was the most downregulated circRNA upon acquired resistance. The depletion of ciRS-7 correlated with increased methylation levels of the promoter CpG island of its host gene, LINC00632. Expression of LINC00632 and ciRS-7 was partly restored by treatment with a combination of an EZH2 inhibitor (EPZ-6438) and a DNA methyl transferase inhibitor (5-azacytidine), which also restores the IMiD sensitivity of the cells. However, knockdown of ciRS-7 did not affect IMiD sensitivity and we found that ciRS-7 also becomes epigenetically silenced after prolonged cell culture without drug-exposure. In conclusion, we found that genome-wide circRNA expression patterns reflect IMiD sensitivity in an in vitro model of acquired resistance.

Original languageEnglish
JournalCancers
Volume13
Issue number3
ISSN2072-6694
DOIs
Publication statusPublished - 20 Jan 2021

    Research areas

  • Circular RNA, Epigenetics, Genome-wide profiling, Immunomodulatory drugs, Multiple myeloma, Non-coding RNA, RNA-sequencing, multiple myeloma, non-coding RNA, genome-wide profiling, epigenetics, circular RNA, immunomodulatory drugs

ID: 62073433