Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.7.48 (
transcriptase
)
9,479
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The
REV3L
gene, encoding the catalytic subunit of human polymerase zeta, plays a significant role in the cytotoxicity, mutagenicity, and chemoresistance of certain tumors. However, the role of
REV3L
in regulating the sensitivity of glioma cells to chemotherapy remains unknown. In this study, we investigated the expression of the
REV3L
gene in 10 normal brain specimens and 30 human glioma specimens and examined the value of
REV3L
as a potential modulator of cellular response to various DNA-damaging agents. Reverse
transcriptase
PCR/real-time PCR analysis revealed that
REV3L
was overexpressed in human gliomas compared with normal brain tissues. A glioma cell model with stable overexpression of
REV3L
was used to probe the role of
REV3L
in cisplatin treatment; upregulation of
REV3L
markedly attenuated cisplatin-induced apoptosis of the mitochondrial apoptotic pathway. We therefore assessed the
REV3L
-targeted treatment modality that combines suppression of
REV3L
expression using RNA interference (RNAi) with the cytotoxic effects of DNA-damaging agents. Downregulation of
REV3L
expression significantly enhanced the sensitivity of glioma cells to cisplatin, as evidenced by the increased apoptosis rate and marked alterations in the anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl) and proapoptotic Bcl-2-associated x protein (Bax) expression levels, and reduced mutation frequencies in surviving glioma cells. These results suggest that
REV3L
may potentially contribute to gliomagenesis and play a crucial role in regulating cellular response to the DNA cross-linking agent cisplatin. Our findings indicate that RNAi targeting
REV3L
combined with chemotherapy has synergistic therapeutic effects on glioma cells, which warrants further investigation as an effective novel therapeutic regimen for patients with this malignancy.
...
PMID:REV3L confers chemoresistance to cisplatin in human gliomas: the potential of its RNAi for synergistic therapy. 1928 90
