OncomiRs: the discovery and progress of microRNAs in cancers.
microRNAs (miRNAs) are evolutionarily conserved, endogenous, small, noncoding RNA molecules of about 22 nucleotides in length that function as posttranscriptional gene regulators. They are deemed to play a crucial role in the initiation and progression of human cancer, and those with a role in cancer are designated as oncogenic miRNAs (oncomiRs). For example, miR-15 and miR-16 induce apoptosis by targeting Bcl2. miRNAs from the miR-17-92 cluster modulate tumor formation and function as oncogenes by influencing the translation of E2F1 mRNA. miR-21 modulates gemcitabine-induced apoptosis by phosphatase and tensin homolog deleted on chromosome 10-dependent activation of PI 3-kinase signaling. miR-34a acts as a suppressor of neuroblastoma tumorigenesis by targeting the mRNA encoding E2F3 and reducing E2F3 protein levels. The chromosomal translocations associating with human tumors disrupt the repression of High mobility group A2 by let-7 miRNA. In addition, the oncomiRs expression profiling of human malignancies has also identified a number of diagnostic and prognostic cancer signatures. This article introduces the roles of oncomiRs in neoplasm development, progression, diagnosis, prognostication, as well as their mechanism of actions on target mRNAs and the functional outcomes of their actions on mRNAs. The paper ends with a brief perspective to the future of oncomiRs.
Cho
William C S
WC
Department of Clinical Oncology, Queen Elizabeth Hospital, Room 1305, 13/F, Block R, 30 Gascoigne Road, Kowloon, Hong Kong SAR, PR China. chocs@ha.org.hk
D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics*; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D046228:Microarray Analysis; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D009857:Oncogenes; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012334:RNA, Neoplasm; D025521:Tumor Suppressor Proteins