Roles of miRNA dysregulation in the pathogenesis of multiple myeloma

Abstract

Multiple myeloma (MM) is a malignant disease of plasma cells with complex pathology, causing significant morbidity due to its end-organ destruction. The outcomes of patients with myeloma have significantly improved in the past couple of decades with the introduction of novel agents, such as proteasome inhibitors, immunomodulators, and monoclonal antibodies. However, MM remains incurable and presents considerable individual heterogeneity. MicroRNAs (miRNAs) are short, endogenous noncoding RNAs of 19–22 nucleotides that regulate gene expression at the posttranscriptional level. Numerous studies have shown that miRNA deregulation is closely related to MM pathology, including tumor initiation, progression, metastasis, prognosis, and drug response, which make the complicated miRNA network an attractive and marvelous area of investigation for novel anti-MM therapeutic approaches. Herein, we mainly summarized the current knowledge on the roles of miRNAs, which are of great significance in regulating pathological factors involved in MM progressions, such as bone marrow microenvironment, methylation, immune regulation, genomic instability, and drug resistance. Meanwhile, their potential as novel prognostic biomarkers and therapeutic targets was also discussed.

Effect of Autologous Stem Cell Transplantation Combined with Modified VTD Regimen on Elderly Patients with Multiple Myeloma and Its Influence on miRNA Cytokines

“…The change of miRNA expression level can be used to monitor the progress of multiple myelom, and can also be used as a marker for diagnosis of multiple myeloma. At present, some studies have shown that miRNA-21 is closely related to the occurrence, invasion, metastasis, and drug resistance of tumors, and some studies have taken miRNA as a gene therapy target for multiple myeloma [11][12][13]. Many patients with multiple myeloma have immune dysfunction, and their gene subtypes and chromosomal abnormalities are related to certain miR-NAs, and more than 50% of miRNAs are located in genomic regions such as amplification region, cleavage site, fragile site, and loss of heterozygosity.…”

Long non‐coding RNA OIP5‐AS1 (Cyrano): A context‐specific regulator of normal and disease processes

“…Multiple myeloma is a haematological malignancy where abnormal expression or dysregulation of miRNAs have been found 127,128 . OIP5‐AS1 has been implicated in the progression of multiple myeloma and the prognosis for multiple myeloma patients via different mechanisms involving miRNAs 7,129 …”

Effects of the SLCO1B1 A388G single nucleotide polymorphism on the development, clinical parameters and survival of multiple myeloma cases in a Polish population

“…MM is characterized by the clonal B-cell proliferation in bone marrow typically associated with overproduction of monoclonal proteins that accumulate in serum and urine 2 . The clonal expansion of monotypic plasma cells in the bone marrow is often associated with excessive production/secretion of monoclonal protein into the blood 3 . The development of multiple myeloma causes a variety of clinical symptoms, including anemia, hypercalcemia, immune paresis, and organ damage such as kidney and bone disorders 2,3 .…”

“…Multiple myeloma is one of the most common hematological malignancies in adults worldwide and accounts for 1.8% of all cancer cases and approximately 10% of hematologic malignancies 3,4 . In Europe there are more than 48,000 new cases and around 31,000 deaths each year 5,6 .…”

“…Over the past two decades, strategies for MM therapy have rapidly evolved and led to improved outcomes including prolonged survival, mainly due to availability and application of new drugs and their combinations with limited toxicity, such as: proteasome inhibitors, immunomodulators, and monoclonal antibodies 2,3,9 . Nevertheless, the disease is considered incurable and displays signi cant heterogeneity in clinical presentation, course and survival 10 .…”