Abstract
Cancer is a complex disease in which unrestrained cell proliferation results in tumour development. Extensive research into the molecular mechanisms underlying tumorigenesis has led to the characterization of oncogenes and tumour suppressors that are key elements in cancer growth and progression, as well as that of other important elements like microRNAs. These genes and miRNAs appear to be constitutively deregulated in cancer. To identify signatures of miRNA-mRNA interactions potentially conserved in essential cancer pathways, we have conducted an integrative analysis of transcriptomic data, also taking into account methylation and copy number alterations. We analysed 18,605 raw transcriptome samples from The Cancer Genome Atlas covering 15 of the most common types of human tumours. From this global transcriptome study, we recovered known cancer-associated miRNA-targets and importantly, we identified new potential targets from miRNA families, also analysing the phenotypic outcomes of these genes/mRNAs in terms of survival. Further analyses could lead to novel approaches in cancer therapy.
Highlights
Unrestrained cell proliferation is the principal hallmark of cancer, provoked by DNA insults and other events
These are single stranded non-coding RNAs of 19–22 nucleotides commonly involved in mRNA destabilization and degradation10,11. miRNAs from the same family share a high degree of sequence homology and they are commonly found in clusters, the components of which are expressed simultaneously, in turn resulting in a tendency to regulate genes with similar functions[12]
The inappropriate expression of miRNAs that regulate key genes like oncogenes or tumour repressor genes can lead to tumour development, and families such as miR-15, miR-1 and let-7 have frequently been related with cancer growth and metastasis
Summary
Unrestrained cell proliferation is the principal hallmark of cancer, provoked by DNA insults and other events These insults produce mutations in genes that might alter their expression and/or function, deregulating many physiological pathways and provoke chromosomal damage, events that drive oncogenic transformation and tumour progression[1]. The role of microRNAs (miRNAs) in cancer and in cell proliferation has gained significance given their critical role in regulating target genes These are single stranded non-coding RNAs of 19–22 nucleotides commonly involved in mRNA destabilization and degradation. Its over-expression is related to E2F113 and AIB114 down regulation, which in turn produces tumours by inducing cell growth and proliferation There is another subset of miRNAs, the tumour suppressor miRNAs or anti-oncomiRs, among which we can distinguish the miR-143/145 cluster that is transcribed as a bicistronic unit. The miR-143/145 cluster targets a large number of genes and their deregulation is thought to be one of the earliest events in cancer development[16]
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