cleavage occurs via the endoribonuclease Dicer to generate the
mature miRNAs [17]. Mature miRNAs can associate with one of
Argonaute (AGO) proteins to form an RNA-induced silencing
complex (RISC) and guide translational repression of fully or par-
tially complementary target mRNAs [18]. Mature miRNAs can also
be released by the cells after binding to proteins such as Argonaute-
2[19] or lipoproteins [20] or loading in the microvesicles [21]
formed by plasma membrane blebbing. Alternatively, miRNAs can
be associated with exosomes that are released by exocytosis
[21]. Figure1 shows the biogenesis and release of miRNAs.
MiRNAs are involved in many biological processes, including
cellular differentiation, metabolism, and cancer development
[22, 23]. Their modes of dysregulation are related to many diseases
[24]. In attempts to identify novel early biomarkers of T2D, most
of the miRNA expression profiling studies were performed in
cultured cells, blood, or solid tissue samples [25–28]. A large
number of miRNAs were identified to be differentially expressed,
either overexpressed or underexpressed, while only a small number
would be important signatures or therapeutic targets. It is, there-
fore, challenging to determine which miRNAs are potential bio-
markers; which miRNAs are tissue-specific; whether circulating
miRNAs make the best biomarkers; and whether animal models
are sufficient for pilot studies. The results from these studies are,
however, subject to rigorous evaluation for consistency and repro-
ducibility by meta-analysis. Academic laboratories provide onlyFig. 1Biogenesis and release of miRNAs
MicroRNA Meta-analysis 475