The Application of MicroRNAs in Cancer Diagnostics - RNA Interference from Biology to Therapeutics - page 278

in squamous cell carcinoma [ 155 ], and miR-195 and let-7a in breast cancer patients
[ 203 ] were significantly reduced after surgical removal of the tumor tissues. For
hepatocellular carcinoma, a decreased level of miR-92a relative to miR-638 was
observed among cancer patients [ 208 ]. After surgical removal of the tumor, the
miR-92a/miR-638 level was restored with borderline significance. Future studies
may show whether sustained or subsequent rise of a cancer-specific circulating
miRNA can point to disease relapse. Downregulation of circulating miR-92 in
plasma has been observed in patients with acute leukemia [ 211 ] . The cellular origin
of the normal levels of miR-92a is unknown and it remains speculative why this
miRNA is downregulated in cancer. In addition to profiling of serum and plasma, a
recent study utilized bile for the identification of miR-9 as a potential circulating
biomarker for biliary tract cancer [ 200 ]. In urine, four miRNAs (miR-96, miR-183,
miR-126, and miR-182) have been associated with bladder cancer and disease stage
and progression [ 201, 202 ]. Future studies are likely to incorporate additional body
fluids for the identification of circulating miRNAs with diagnostic and prognostic
potential.

13.5 Long Non-coding RNAs with Potential

in Cancer Diagnostics

13.5.1 Long Non-coding RNAs are Deregulated

in Cancer and Modulate Gene Expression

Although miRNAs constitute the largest group of non-coding RNAs (ncRNAs)
known to be involved in cancer development and progression, other classes of
ncRNAs with great potential for cancer prognosis and diagnosis including various
long non-coding RNAs (lncRNAs) are currently being discovered. lncRNAs consti-
tute a large group of RNA transcripts, which are more than 200-nt long, not trans-
lated into protein, and may or may not be poly-adenylated and spliced. A consensus
annotation system for lncRNAs does not yet exist, as new molecules are continu-
ously discovered. Genes for lncRNAs can be found in intergenic regions, within
introns of protein coding genes (intragenic) as well as overlapping with exons of
protein coding genes. lncRNAs are expressed in all human cell types and can be
purified using standard mRNA purification protocols. The remaining part of this
section describes lncRNAs in relation to cancer in more detail.
Although the biological functions are not fully understood, some long ncRNAs
are known to play important roles in regulation of gene expression. For example, a
number of newly discovered large intergenic non-coding RNAs (lincRNAs) have
been shown to repress gene transcription by targeting polycomb repressor complex
1 (PRC1) or 2 (PRC2) to specific genes (reviewed in [ 234, 235 ] ). PRCs regulate
gene expression via chromatin modifications and are known to be involved in main-
taining pluripotency of embryonic stem cells by repressing developmental genes