MicroRNAs and Cancer: Perspective on the Discovery and Function

Non-coding RNA transcripts likely outnumber the group of protein coding sequences andhold promise of many new discoveries and mechanistic explanations for essential biologicalphenomena and pathologies. The best characterized non-coding RNA family consists inhumans of about 1880 microRNAs. MicroRNAs (miRNAs) are short non-coding RNAs of20†24 nucleotides that play important roles in virtually all biological pathways in mammalsand other multicellular organisms. Accordingly, miRNAs influence numerous cancer-relevantprocesses such as proliferation, cell cycle control, apoptosis, differentiation, migration andmetabolism. Since their discovery, twenty-two years ago, the knowledge on miRNAs andcancer has been increasing exponentially (>18,500 hits in PubMed accessed in June 2015).With the advent of next generation sequencing techniques a previously unknown world ofmiRNAs molecules have been discovered. More study focused on miRNAs roles in cancerwith different ways such as: Genetic alterations, Epigenetic mechanisms, Regulation ofmiRNAs by transcription factors in cancer, miRNA suppression by oncogenic transcriptionfactors, miRNA downregulation by loss of tumour suppressor transcription factors andMutations in miRNA biogenesis pathways. Till now, main mechanisms for escape frommiRNAs to cancer contain mutations in miRNA target sites, alternative splicing orpolyadenylation, target site exclusion on mRNA, Competition for miRNA binding by otherendogenous RNAs, Cell cycle and proliferation control, miRNA regulation of senescence,miRNAs in DNA damage responses. As the important roles of miRNAs in cancer are beingdeciphered their potential as prognostic or diagnostics markers is evidenced by a long list ofstudies. Furthermore, therapeutics strategies involving re-introduction of miRNAs lost incancer or inhibition of oncogenic miRNAs are rapidly being developed. Our understanding ofthe functions of the majority of miRNAs comes only from those studies in cell culture modelsand clearly we must explore their dependency on cellular context and study their interplaywithin prevalent cancer lesions. The next decade should be interesting too.

کلیدواژه ها:

MicroRNA ، Cancer ، Non-coding RNA ، Genetic alterations ، Next Generation Sequencing (NGS)