Abstract
The discovery of the biological relevance of non-coding RNA (ncRNAs) molecules represents one of the most significant advances in contemporary molecular biology. Expression profiling of human tumors, based on the expression of miRNAs and other short or long ncRNAs, has identified signatures associated with diagnosis, staging, progression, prognosis, and response to treatment. In this review we will discuss the recent remarkable advancement in the understanding the biological functions of human ncRNAs in cancer, the mechanisms of expression and the therapeutic potential.
Highlights
The human genome sequencing performed by the International Human Genome SequencingConsortium revealed that the number of protein-coding genes corresponded only to 20–25,000 [1].While, at first, it was common belief that the remaining, bigger portion of the human genome was not functional and considered as “junk DNA”, several studies based on advanced technologies such as tiling arrays and RNA deep sequencing have recently pointed out the identification of thousands of RNA transcripts not derived from known genes and not encoding for a protein [2,3]
Zhang and colleagues [70] showed that miR-21 induced growth and invasion in non-small cell lung cancer by repressing PTEN; miR-21 modulate tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) sensitivity in glioma cells mainly by modulating caspase-3 and TAp63 expression and TRAIL-induced caspase machinery [71], confirming that miR-21 acts like an oncogene by blocking the expression of critical apoptosis-related genes
The oncomiR group is wide, and comprises other microRNAs such as the miR-17-92 cluster, which is crucial for B-cell proliferation and its absence induces an increase of the proapoptotic protein Bim and inhibits the pro-B to pre-B cell development [85]; miR-372/373, which are involved in the development of human testicular germ cell tumors by neutralizing the TP53 pathway [86]; miR-10b, which promotes cell migration and invasion in breast cancer [87]; the polycistron miR-106-25, which acts as an oncogene by interfering with the synthesis of p21 and Bim [88]
Summary
The human genome sequencing performed by the International Human Genome Sequencing. Consortium revealed that the number of protein-coding genes corresponded only to 20–25,000 [1]. PIWI-family proteins and their associated small RNAs (piRNAs) provide an essential protection for germ-cell genomes against the activity of transponsable elements (TE). They help to maintain genome integrity, silencing TE [4] and this role is highly conserved across animal species. The levels of piR-823 were positively associated with TNM stages and distant metastasis, suggesting that piR-823 should be tested as a biomarker for detecting circulating gastric cancer cells in the blood [41] All these data may suggest an important role of the axis PIWI and PIWI-associated RNAs going beyond the regulation of the genome in germline tissues and more studies are needed in order to investigate their specific role in tumorigenesis
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