The Application of MicroRNAs in Cancer Diagnostics - RNA Interference from Biology to Therapeutics - page 280

Since the UCRs are merely conserved genomic sequences, they are unlikely to be
all involved in the same cellular functions. However, many of the T-UCRs have been
shown to harbor enhancer functions [ 249 ]. T-UCR expression is deregulated in can-
cer, and different types of cancer are associated with specific expression signatures
of the T-UCRs [ 247, 248 ]. The mechanisms behind deregulation of T-UCRs in can-
cer may involve epigenetic aberrations [ 250 ] , genomic rearrangements [ 247 ] , or
miRNA-mediated degradation [ 247 ]. Thus, T-UCR expression as well as changes in
DNA methylation and/or larger scale DNA alterations may have potential as cancer
biomarkers. This is illustrated in a number of malignancies. In neuroblastoma, high
expression of 28 T-UCRs, which correlate negatively with specific miRNAs, is
associated with a good prognosis [ 251 ]. Moreover, in hepatocellular carcinoma,
expression levels of 56 T-UCRs are deregulated [ 252 ]. In colorectal cancer and
lymphocytic leukemia, cancer-associated sequence abnormalities in UCRs have
been reported [ 253 ]. Furthermore, in a collection of different types of primary
tumors, three specific T-UCRs (Uc.160+, Uc.283 +A, and Uc.346+) are downregu-
lated by DNA methylation, which is associated with the formation of lymph node
metastases [ 250 ]. Although these observations need further validation, they all seem
to be of potential use in future cancer diagnostics.

13.5.2 PCA3 and Examples of Other lncRNAs as Potential

Cancer Diagnostics

Prostate Cancer Antigen 3 (PCA3) is a non-coding RNA that can be found in urine
from prostate cancer patients. It has been developed as a diagnostic biomarker for
prostate cancer and is now commercially available (reviewed in [ 254 ] ). The cellular
function of PCA3 has not been fully clarified, but several reports suggest that PCA3
regulates the transcript level of its host gene BMCC1/PRUNE2 (Prune homolog 2)
(reviewed in [ 255 ]). Numerous studies have evaluated the sensitivity and specificity
of PCA3 for prostate cancer detection in urine (reviewed in [ 254 ] ). Together, results
from these studies indicate that PCA3 may not be the ideal biomarker in urine, pri-
marily, because it does not clearly reflect the abundance of PCA3 in the tumor
where PCA3 is frequently overexpressed [ 256- 258 ] . Nevertheless, in combination
with the routinely used serum biomarker PSA, a urine test for PCA3 may be added
to increase the specificity of diagnosis.
Vault non-coding RNAs (vRNAs) are components of vault ribonucleoprotein
complexes, which confer drug resistance in cancer cells. Three vRNAs, highly similar
in sequence and secondary structure, are known to be expressed in mammalian
cells. Overexpression of vRNAs in cancer cell lines confers chemoresistance, while
knock-down of vRNAs renders cancer cells more sensitive to chemotherapeutics
[ 259 ]. Hence, the expression status of vault RNAs in cancer cells may aid in predic-
tion of resistance to chemotherapeutic compounds.