Biomedical Engineering Reference
In-Depth Information
A)
Extrinsic Factors
Transcription
Factors
miRNAs
Protein
Gene
B)
Extrinsic Factors
miRNAs
(TS)
Transcription
Factors
Oncogene
(OG)
Protein
C)
Extrinsic Factors
miRNAs
(OG)
Transcription
Factors
Tumor Suppressor
(TS)
Protein
Fig. 3 Cancer and miRNA. The cellular identity is maintained by expression of a network of
transcription factors (partly in response to extrinsic factors) and their contribution to the
signature expression profiles of protein-coding genes as well as miRNAs. The arrows with
broken lines represent either activation or repression of target genes by a network of
transcription factors. (A) Regulation of miRNAs and their involvement in incoherent feed-
forward regulation (observed in embryonic stem cells, Fig. 2) (Marson et al., 2008). (B) If the
targets of miRNAs are oncogenes (OG), the miRNAs are defined as a tumor suppressor (TS)
miRNAs. Loss of function for these miRNAs (shown by downward arrow) thus may result in
tumor formation. (C) If the targets of miRNAs include tumor suppressor genes, these
miRNAs are defined as oncogenic miRNAs or onco-miRs. Gain of function of these
miRNAs (shown by upward arrow) may thus result in tumor formation
expression of miRNAs have been proposed as one of the early events in the
pathogenesis of CLL (Calin et al., 2002).
In recent years, the expression profiling of miRNA genes has emerged as a
potent tool for classification, diagnosis, grading, prognosis, and treatment
outcome assessment in various cancers (Calin and Croce, 2006; Calin et al.,
2005; Yanaihara et al., 2006). Stage I lung cancer has been shown to be tightly
correlated with the expression profile of a small group of miRNA genes
(Yanaihara et al., 2006). Expression profiles of miRNAs in CLL can distinguish
between benign and aggressive tumors. Processing defects due to mutations in
precursor miRNA molecules lead to the deregulation of specific miRNAs in
CLL (Calin et al., 2005). The amplification of the region harboring a miRNA
gene, loss of or deregulation of transcription factors, and loss of methylated
CpG islands in promoter regions may lead to activation of miRNA expression.
Chromosomal translocation in chromosome 11q23 in acute lymphoblastic
