Investigation of MiR-21, MiR-32 and MiR-181a/b in terms of Treatment Response in Multiple Myeloma

Abstract

Introduction/AimMultiple myeloma (MM) is a B-cell neoplasm characterized by the proliferation of clonal malignant plasma cells in the bone marrow. The incidence rate is higher in leukemia and hematologic system comes second after lymphoma among malignant tumors and constitutes about 15% of all haematological cancers. Despite the identification of new drugs such as thalidomide, bortezomib, and lenalidomide, which result in a higher overall response rate and longer life span in MM treatment, MM is still an untreatable disease.MicroRNAs (miRNAs) play a role in critical biological processes such as cell differentiation, apoptosis and cell proliferation in cancer. Recent studies have identified miRNA profiles in human myeloma cell lines and primer patient specimens, and these miRNA expression patterns have been associated with specific genetic anomalies and the patient's surveillance. The aim of this thesis work was to examine that difference in expression levels of the 4 miRNAs (miR-21, miR-32, miR-181a and miR-181b) associated with response to treatment.Material and methodsThe level of expression of (miR-21, miR-32, miR-181a and miR-181b genes) in cells of Multiple Myeloma patients, RNA samples that obtained from whole blood samples of 38 MM patients (pre-treatment and post-treatment) and healthy control groups were investigated the expression pattern of miRNAs using Real-Time PCR technique.Results The comparison of MM group with healthy controls revealed upregulation of 4 miRNAs levels before starting of chemotherapy treatment, and after treatment there were decreased in these levels as response in treatment, but some patients showed non-response effect to treatment. In chemotherapy response group, the length of time free from MM disease was associated with decreased miR-32 Expression levels as a result of treatment response. Conclusion miR-21, miR-32, miR-181a and miR-181b regulate cell differentiation, proliferation, apoptosis and participate in vascular invasion and metastasis of tumor cells.

We believe that the inhibition of miR-21, miR-32, miR-181a and miR-181b in future experiments with anticancer drugs, and the investigation of whether drug activity develops if these microRNAs are inhibited can also contribute to both the patient's benefit and the literature.