MicroRNA and drug resistance(review).pdfVIP

REVIEW MicroRNA and drug resistance J Ma, C Dong and C Ji Department of Hematology, Qilu Hospital, Shandong University, Jinan, Shandong, China Chemotherapy is the preferred treatment for malignancies. However, a successful long-term use of chemotherapy is often prevented by the development of drug resistance. Many mechanisms such as gene mutation, DNA methylation and histone modification have important roles in the resistance of cancer cells to chemotherapeutic agents. Climent suggested miR-125b was involved in the development of drug resistance by microRNA (miRNA) dysregulation. miRNAs are endogenously expressed small non-coding RNAs, which are evolutionarily conserved and function as regulators of gene expression. Much effort has been exerted in analyzing the role of miRNAs in the development of drug resistance in a variety of malignancies. Several research groups have shown that the expressions of miRNAs in chemoresistant cancer cells and their parental chemosensitive ones are different. The molecular targets and mechanisms of chemosensitivity and chemoresistance are also elucidated. This article reviews the functions of miRNAs in the development of drug resistance. Cancer Gene Therapy (2010) 17, 523–531; doi:10.1038/cgt.2010.18; published online 14 May 2010 Keywords: review; microRNA; drug resistance; cancer Introduction MicroRNAs (miRNAs) are a new class of small, non- protein-encoding RNAs that range in size from 19 to 25 nucleotides (nt) and have important roles in a variety of biologic processes.1,2 Like conventional protein-coding mRNA, miRNAs are transcribed by RNA polymerase II, spliced, capped and poly-adenylated (called primitive miRNA or pri-miRNA). Then primitive miRNA tran- scripts are processed by a RNase III endonuclease, Drosha, to the hairpin ‘precursor’ miRNAs that are B70 nt in animals or B100 nt in plants in the nucleus.3 This hairpin precursor miRNA bounds to exportin-5 and RNA GTPase, which allows the transport of the molecules into the cyto