Abdi Jahangir, Jian Hou, Chang Hong
Division of Molecular and Cellular Biology, Toronto General Research Institute, Toronto, Ontario, Canada.
Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Oncotarget. 2016 Sep 13;7(37):60723-60735. doi: 10.18632/oncotarget.11032.
While novel therapeutic approaches have profoundly improved survival of multiple myeloma (MM) patients, drug resistance and treatment refractoriness still persists. This obstacle highly demands thorough investigation into the root and underlying molecular mechanisms to develop more effective strategies. The advent of micro-RNAs (miRNAs) in the study of cancer biology and pathogenesis in recent years has revolutionized therapy in this field and particularly opened new windows to further understanding of tumor drug resistance. However; in spite of the fact that miRNAs involvement in MM pathogenesis and progression has been substantially evidenced, miRNA investigation in MM drug resistance is still in its infancy. Our knowledge of the potential role of miRNAs in MM drug resistance comes from few recent reports confirming that some miRNAs including miR-137/197, miR-21 and miR-221/222 could negatively modulate drug sensitivity of MM cells. Further continuous researches are required to exploit miRNAs to elucidate the critical mechanisms controlling drug resistance in MM. In this review, we will highlight the most recent observations on the role of miRNAs in MM drug resistance. Moreover, approaches and insights into clinical application of miRNAs to overcome MM drug resistance will be discussed.
尽管新型治疗方法显著提高了多发性骨髓瘤(MM)患者的生存率,但耐药性和治疗难治性仍然存在。这一障碍迫切需要深入研究其根源和潜在分子机制,以制定更有效的策略。近年来,微小RNA(miRNA)在癌症生物学和发病机制研究中的出现,彻底改变了该领域的治疗方法,尤其为进一步理解肿瘤耐药性打开了新窗口。然而,尽管miRNA参与MM发病机制和进展已有大量证据,但miRNA在MM耐药性方面的研究仍处于起步阶段。我们对miRNA在MM耐药性中潜在作用的了解来自最近的一些报道,这些报道证实包括miR-137/197、miR-21和miR-221/222在内的一些miRNA可负向调节MM细胞的药物敏感性。需要进一步持续研究以利用miRNA阐明控制MM耐药性的关键机制。在本综述中,我们将重点介绍miRNA在MM耐药性中作用的最新观察结果。此外,还将讨论miRNA克服MM耐药性的临床应用方法和见解。