Association of miRNAs with Pathogenesis - Therapeutic Strategies in Cancer Biology and Pathology - page 3

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Association of miRNAs with
Pathogenesis

It is continually being recognised that non-coding RNAs including miRNAs might
be associated with the pathogenesis of human diseases; among them are neurologi-
cal and cardiovascular conditions, developmental abnormalities and tumour devel-
opment and dissemination (Esteller, 2011). The participation of miRNAs in these
processes has been anticipated by their involvement in cell proliferation, apoptosis,
determination of cell lineage in haematopoiesis, neuronal patterning, among others,
in various living systems ( Table 2.1 ).

The Genesis of DiGeorge Syndrome

DiGeorge syndrome is a congenital condition resulting from defects in chromo-
some 22, more precisely a 22p11.2 deletion syndrome. The 22q11.2 microdeletion
has been reported to occur with altered neurodevelopment and associated cogni-
tive, behavioural and psychiatric disorders, cardiac abnormalities, deficiency of the
immune system and proneness to infection, autoimmune conditions, abnormalities of
the palate and parathyroid dysfunction (Philip and Bassett, 2011; Halder et al., 2010;
Machado et al., 2010; Tison et al., 2011; Veerapandiyan et al., 2011). A vast majority
of patients with DiGeorge syndrome show monoallelic deletion of 22q11.2 in 1/3000
live births (Shiohama et al., 2003), and further the deleted chromosomal region hap-
pens to contain the DGCR8 gene. But needless it would be to say a number of other
genes related to developmental processes might be affected by the deletion. Of note
in terms of elucidation of the modes of genesis of human disease is the perceived
correlation between miRNAs and incidence of DiGeorge syndrome.

Association of the Glyoxalase Pathway with miRNA Function

Glyoxalase I (GLO1) has been attributed with anti-glycation mediated protection
of cells. GLO1 together with glyoxalase II form the glyoxalase system which is an
important route to break down of reactive free radicals and detoxification. GLO1
is highly expressed in many tumours, for example, colon, breast and prostate can-
cer (Ranganathan et al., 1993; Rulli et al., 2001; Davidson et al., 1999). In the past
5 years overexpression of glyoxalase 1 has been reported in melanoma (Bair et al.,
2010) and pancreatic cancer (Wang et al., 2012d). Fonseca-Sanchez et al. (2012)
found that GLO1 expression in breast cancer was associated with tumour stage.