Potential Role of microRNAs in inducing Drug Resistance in Patients with Multiple Myeloma

Abstract

The prognosis for newly diagnosed subjects with multiple myeloma (MM) has significantly progressed in recent years. However, most MM patients relapse and after several salvage therapies, the onset of multidrug resistance provokes the occurrence of a refractory disease. A continuous and bidirectional exchange of information takes place between the cells of the microenvironment and neoplastic cells to solicit the demands of cancer cells. Among the molecules serving as messengers, there are microRNAs (miRNA), a family of small noncoding RNAs that regulate gene expression. Numerous miRNAs are associated with drug resistance, also in MM, and the modulation of their expression or activity might be explored to reverse it. In this review we report the most recent studies concerning the relationship between miRNAs and chemoresistance to the most frequently used drugs, such as proteasome inhibitors, steroids, alkylating agents and immunomodulators. The experimental use of antagomirs or miRNA mimics have successfully been proven to counteract chemoresistance and display synergistic effects with antimyeloma drugs which could represent a fundamental moment to overcome resistance in MM treatment.

Specialized Intercellular Communications via Tunnelling Nanotubes in Acute and Chronic Leukemia

“…Moreover, resistance to tumor treatment is still a critical problem, causing relapse and decreased overall survival. Several mechanisms that promote chemoresistance have been reported [92,93], and it is recognized that aggressive aptitudes and chemoresistance are correlated to the augmented communication function in tumor cells, and TNTs could have an effect in the onset of chemoresistance. Mitochondrial transfer may induce chemoresistance through different systems, comprising the inhibition of programmed cell death, the decreased production of ROS, and the increased salvaging of cells with altered mitochondria [94].…”

“…Furthermore, it was reported that TNT signaling from MSCs to ALL cells might also provoke the chemoresistance of leukemic cells (Figure 4). For example, TNTs have been reported to transfer drug efflux pumps, such as P-glycoproteins, toward tumor cells [92].…”

Multiple Myeloma: Challenges Encountered and Future Options for Better Treatment

“…miRNAs can function as oncogenic or suppressors of tumors. It has been reported that miRNAs may control the drug response of MM cells through regula-tion of the apoptotic or proliferative pathways, which include p53 [46], which is a transcription factor that can stimulate tumor suppressor miRNAs or even inhibit some on-comiRNAs [47]. The miRNAs activated by p53 have been reported to affect the antiapoptotic genes, thereby enhancing the tumor suppressor activity of p53 [47].…”

Circular RNA as a Novel Biomarker for Diagnosis and Prognosis and Potential Therapeutic Targets in Multiple Myeloma

“…In spite of the progress with antimyeloma therapy, the occurrence of chemoresistance is still the main reason for MM relapse [ 78 ]. The conditions causing chemoresistance are composite mechanisms, including increased drug efflux pumps efficacy, reduced drug levels, modification in DNA repair, changes in growth and programmed cell death [ 79 ], and all types of ncRNAs appear to have a relevant effect on the occurrence of MM drug resistance [ 80 ].…”