MicroRNAs in Cancer

Abstract

During the last few years, studies on microRNA (miRNA) and cancer have burst onto the scene. Profiling of the miRNome (global miRNA expression levels) has become prevalent and abundant miRNome data are currently available from various cancers. The pattern of miRNA expression can be correlated with cancer type, stage, and other clinical variables, so that miRNA profiling can be used as a tool for cancer diagnosis and prognosis. miRNA expression analyses also suggested oncogenic (or tumor suppressive) roles of miRNAs. miRNAs play roles in almost all aspects of cancer biology such as proliferation, apoptosis, invasion/metastasis, and angiogenesis. Given that many miRNAs are deregulated in cancers but have not yet been further studied, it is expected that more miRNAs will emerge as players in the etiology and progression of cancer. miRNAs will be also discussed as a tool for cancer therapy. SYNOPSIS During the last decade, a major discovery in biology was the discovery of small RNAs, including miRNA (microRNA) and siRNA (small interfering RNA), as highlighted by the 2002 December issue of Science magazine (1). Since RNA interference (RNAi) phenomenon was discovered in nematodes (2), siRNA has provided a technical breakthrough for short term genetics in mammalian systems. The big impact of small RNAs was well celebrated by the 2006 Nobel prize awarded to the two scientists who discovered RNAi. On the other side, miRNAs shed new insight on the post-transcriptional regulation of gene expression. miRNAs were also first discovered in worms (3, 4), and later in a number of animals, plants, and viruses. During the last couple of years, the miRNA field has been expanding with many recent publications implicating miRNAs in diverse cellular processes. Cancer is a major cause of death in the United States (“Cancer Facts & Figures 2007” from American Cancer Society; http://www.cancer.org/docroot/stt/stt_0.asp). Cancer is a complex genetic disease caused by the accumulation of mutations that lead to deregulation of gene expression and uncontrolled cell proliferation. Given the wide impact of miRNAs on gene expression, it is not surprising that a number of miRNAs have been implicated in cancer. In this review, the links between miRNA and cancer will be comprehensively described and discussed.

Hypoxia-regulated microRNA-210 modulates mitochondrial function and decreases ISCU and COX10 expression

“…miRNAs have roles in almost all aspects of cell biology, and their deregulation has been reported in various diseases, especially cancer (Lee and Dutta, 2009). Recently, a specific group of hypoxia-regulated miRNAs that are under the regulation of HIF-1a was identified.…”

CXCR4 downregulation of let-7a drives chemoresistance in acute myeloid leukemia

“…The discovery of miRNAs in the early 1990s opened a new era in understanding transcriptional and posttranscriptional regulation of gene expression in biological processes (11)(12)(13). miRNAs are now known to play roles in almost all aspects of cancer biology, including proliferation, apoptosis, invasion and metastasis, and angiogenesis (14)(15)(16). In recent years, functional and prognostic studies have confirmed that miRNAs plays an active role in hematologic malignancies, and some miRNAs have been proposed as prognostic markers and therapeutic targets in leukemia treatment.…”

Cyclin T2: A novel miR‐15a target gene involved in early spermatogenesis

“…They are thought to play negative regulatory roles posttranscriptionally, causing mRNA cleavage or translation repression, by targeting the imperfect complementary sequences, usually located in the 3 0 -untranslated regions (UTRs) of mRNAs [1]. It has been reported that miRNAs are involved in various biological processes, including the cell cycle, differentiation and tumorigenesis [2][3][4]. Additionally, the temporal and spatial specificity that is frequently associated with development and differentiation is another characteristic of miRNA expression [5,6].…”