The Journal
Curing Oral Cancer by silencing p53R2 gene
The p53R2 gene encodes the smaller subunit of
the enzyme ribonucleotidereductase. This gene
is expressed upon stress such as during the
damage of DNA. The p53R2 gene product
causes an increase in the deoxynucleotide
triphosphate (dNTP) pool in the nucleus, which
facilitates DNA repair and synthesis. From
recent research it has been found that p53R2 is
a good molecular target for cancer gene
therapy(5). In this study, three human oral
cancer cell lines (SAS, HSC-4 and Ca9-22)
were tested. The expression of p53R2 is
silenced with the highly specific post-
transcriptional suppression of RNAi. The
expression of p53R2 is investigated with the
reverse transcription-polymerase chain
reaction (RT-PCR) and Western blotting. The
sensitivity to anticancer agents was evaluated
by a 3-(4,5-dimethylthiazol-2-yl)-2,5-
diphenyltetrazolium bromide (MTT) assay.
These results suggest that basal transcription
of p53R2 could be associated with the
sensitivity to anticancer agents. It has also been
found that the inhibition of the expression of
p53R2 gene by the process of RNAi in oral
cancer cells not only prevents their further
growth but also increases their sensitivity
towards 5-fluorouracil (5-FU), a
chemotherapeutic agent . Hence an RNAi
therapy followed by chemotherapy using 5-FU
can be a successful cure for oral cancer .
RNAi screening for novel biomarkers from
human oral cancer
It has been found from research that kinases
and phosphatases are important regulators of
cell survival and apoptosis, respectively.
Hence, discoveries of the novel genes (e.g.
kinases or phosphatases) responsible for these
aberrant cell behaviors (e.g. cell survival or
death.) will be significantly advance our
understanding of human oral cancer,
subsequently leading to more effective
treatments.
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Recently, RNA interference (RNAi) has become
a powerful new tool to perform loss-of-function
genetic screens in mammalian cells and can
greatly facilitate the identification of
components of cellular signalingpathways.In a
recent research at Taiwan scientists have
employed the “anti-kinome” and “anti-
phosphatome” RNAi subsets to high-
throughput screen and systemically identify the
novel regulators of cell proliferation and cell
death during the progression of oral
cancer.Among 6502 shRNA constructs
(covering 1236 genes), 142 shRNA constructs
targeting 42 genes revealed more than 2-fold
growth promotion on human oral cancer HSC-3
cells(6). These 42 genes were submitted to
further analysis resulting in 3 major putative
molecular pathways: ErbB2/ErbB4-IGF-1
receptor, Insulin receptor, p57 pathways. These
novel regulators may have potential as tumor
suppressors and biomarkers for early diagnosis
of the oral cancer. Besides, these regulators
can be used as markers for detecting the high
risk group of oral cancer.
RNAi targeting urokinase-type plasminogen
activator receptor inhibits metastasis and
progression of oral squamous cell
carcinoma
It has been found that urokinase-type
plasminogen activator receptor (u-PAR) is
overexpressed in many human malignant
tumors including oral squamous cell carcinoma
(OSCC) and plays an important role in a variety
of cancer key cellular events as a versatile
signaling orchestrator. In a recent study
conducted by Zhou et al.,a retroviral vector
expressing u-PAR-specific siRNA was injected
into OSCC xenografts of nude mice to observe
its inhibitory effects on OSCC(7). His data
demonstrates that siRNA targeting u-PAR
markedly suppressed tumor growth, reduced
the expression of proliferation-related gene(Ki-
67) and increased cell apoptosis in OSCC.
More importantly, the mRNA and protein
expression of MMP-2, MMP-9, VEGF-C,
Vol. 14 No. 1
Jan-Apr 2018