Although the aberrant expression of miRNAs in
cancer is a proven fact, the exact causes of its have not yet been fully determined.
For this reason, many
researchers around the world have focused their attention on uncovering of
these mechanisms. Until now, several possible causes have been of
them is chromosomal abnormalities, like miR-15 and miR-16, as previously
mentioned are located in a frequently deleted genomic region in CLL. In
addition to structural genetic alteration, miRNAs expression can be also affected by altered activity of the enzymes involved in
the biogenesis of microRNAs,
like Drosha and Dicer. For instance, down regulation of Drosha and Dicer
complex has been reported in 39% of ovarian cancer patients. Indeed, it seems
that decreased expression of level of Drosha and Dicer complex promotes
cellular transformation and tumourgenesis in vivo. MicroRNA expression can be
also modulated by other miRNAs. For example, mouse miR-709 located in the nucleus preventing from pri-miR-15a/16-1
processing into pre-miR-15a/16-1 by directly binding to
recognition site on pri-miR-15a/16-1. Epigenetic changes are another causes of deregulated
microRNA expression in cancer which is well reported in various literatures.
For example, epigenetic repression of tumor suppressor miR-129-2in endometrial
cancer causes the over expression of the SOX4, an oncogene belonging to the
SRY-related high mobility group box family. Notably, miRNAs can also regulate
the expression of enzymes responsible for epigenetic control
which is complicated the scenario connecting microRNAs
and epigenetics. For instance, it has been determined that miR-143 directly
targets DNA methyltranferase 3A DNMT3A in colorectal cancer. Eventually,
deregulated miRNA expression in cancer can be created as a result of altered
transcription factor activity. For example, miR-34a, as commonly deleted miRNA
in human cancers, is directly transactivated by p53. Furthermore, as expected in
significant number of ovarian cancer patients with p53 mutation, due to the loss
of p53 function decreased expression of the miR-34 family was observed.

Over the recent years, the extensive miRNA
profiling studies have demonstrated that there are significantly differences
between miRNA profiles in cancer cells compared with those in normal cells,
suggesting that they have great potential utility as clinical biomarkers and
can also significantly help to the early detection of cancer. For example, in
ductal adenocarcinoma prior to any phenotypic changes in ducts overexpression
of miR-205 and miR-21 has been reported, implicating that aberrant miRNA
expression is an early event in the development of cancer that can derive a
benefit for early diagnosis of cancers

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