MicroRNA Polymorphisms, MicroRNA Pharmacogenomics and Cancer Susceptibility

William      Xu; Qi      Zhao Wang; Qi      Cui; Ruian      Xu

doi:10.2174/187569210793368221

Abstract

MicroRNAs (miRNAs), a class of short endogenous RNAs, act as post-transcriptional regulators of gene expression. A vast literature has emerged over the past decade about miRNAs and their pivotal roles as negative regulators of gene expression in a wide array of (patho)physiological processes. Recent observations have revealed that many miRNAs are implicated in common human cancers through a variety of mechanisms. miRNA expression can be altered in cancer through chromosomal changes, epigenetic defects, mutations and alterations in the miRNA genes and in the machinery involved in miRNA biogenesis. Detection and monitoring of tumors are now becoming possible by evaluation of tumor-derived secretory miRNAs. Moreover, the term microRNA polymorphisms (miR-polymorphisms) was coined, defined as a novel class of polymorphisms that interfere with the function of a miRNA leading to loss of the miRNAmediated regulation of target genes. miR-polymorphisms can be classified in three major categories: (1) miRpolymorphisms involving the gene silencing machinery; (2) miR-polymorphisms in pri-miRNAs, pre-miRNAs and mat-miRNAs; (3) miR-polymorphisms in miRNA target sites. The new term “miR-pharmacogenomics” can be defined as the study of miRNAs and miR-polymorphisms in their target genes affecting drug behavior in order to improve efficiency of drugs. This paper discusses the recent progress in the field of miR-polymorphisms, miR-pharmacogenomics and their roles in cancer.

Keywords: Cancer, gene therapy, microRNA, personalized medicine, pharmacogenomics, polymorphism, MicroRNAs (miRNAs), chromosomal changes, epigenetic defects, mutations, polymorphisms, Cancer,, Exportin 5 (EPO5), miR-polymorphisms, double-stranded RNA, Tourette syndrome, muscular hypertrophy, ribonucleoprotein, RNA-induced silencing complex (RISC), renal cell carcinoma (RCC), bladder cancer (BDC), premalignant lesion (OPL), RNA interference (RNAi), prostate cancer (PC), hyperplasia, bronchoalveolar carcinomas, adenocarcinoma, tumorigenesis, non small cell lung cancer (NSCLC), lymph node metastasis, papillary thyroid carcinoma (PTC), hepatocellular carcinoma (HC), allele, ovarian cancer (OC), miR-423, miR-26a-1, chronic lymphocytic leukemia (CLL), cervical cancer (CC), estrogen receptor 1 (ESR1 or ERa), -transducin repeat-containing protein (-TrCP), bone morphogenic receptor type 1B (BMPR1B), Integrins, breast carcinoma, dihydrofolate reductase (DHFR), methotrexate (MTX), miR-pharmacogenomics, osteogenic sarcoma, folylpolyglutamate synthase, pediatric leukemia, neoplastic transformation, Drug metabolizing enzymes (DME), transporters (DT), multidrug resistance-associated protein 1 (MRP-1), Pregnane X Receptor (PXR)