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Journal of Gastroenterology and Digestive Diseases | Volume 3
May 25-26, 2018 | New York, USA
World Liver Conference 2018
Background:
NRF2 is ubiquitously expressed transcription
factor regulating cytoprotective genes such as
SOD
, catalase,
TRX
and
GPX
. NRF2 is additionally kenned to be a crucial
regulator of cell survival and oncogenic pathways and is found
to be up-regulated across most cancers. Ergo, investigating
the gene expression status and exome sequencing of
upstream and downstream neighbours of NRF2 is imperative
to understand the oncogenic manifestation central to
NRF2.
RAC1
and GCLC are such upstream and downstream
molecules whose regulation status is unknown across many
cancers.
Methods:
We estimated the GCLC and
RAC1
transcripts from
the RNA isolates from 15 cancer samples of different kinds.
cDNA was constructed and authentic-time quantitative
PCR was performed utilizing SYBR green assay and the fold
change was calculated to understand the regulation status.
Results:
The upstream gene
RAC1
and downstream genes
GCLC were found up-regulated across samples with a
fold change >5 fold. We identified >50 nonsynonymous
deleterious mutations in the 11,416 whole exome cancer
cohort samples. Performing evolutionary profile betokened
no conservancy for the observed mutations.
Discussion:
Integrating the mutations and expression status
of GCLC,
RAC1
and
NQO1
, revealed the up-regulation of
NQO1
due to the activation of the PI3 kinase, and
HMOX1
,
while inactivating of BET and KEAP1 concurrently. Up-
regulation of GCLC designates NF-KB and
HMOX1
to be
activated, while
CYB5R4
and BET are negatively regulated.
The dysregulation of these genes disrupts the free radical
scavenging pathway, cell death and survival pathways, and
anti-apoptotic pathways. These genes are majorly expressed
in the detoxifying organs like liver and kidney. This study
shows that the NRF2 and its upstream molecules are found
to be efficacious biomarkers in the future and early detection
of cancer additionally will come true with these efficient
biomarkers.
Speaker Biography
Mantri Dharaneeswar Reddy has completed his MSc in Genetics (2017) from University
of Mysore, India. His Master’s research focused on the role of NRF2 in ROS and RNS
dependent cancer formation and early detection of cancer. His interest lies in the
continuation of his research on biomarkers for early detection of cancer. He did his
Bachelor’s in Biochemistry at Sri Krishnadevaraya University, India.
e:
mdrmanthri@gmail.comDysregulation of GCLC by NRF2 signalling disrupts anti-oxidant pathway central to most cancers and
RAC1
protein modifications in cancer
Mantri Dharaneeswar Reddy
and
Avinash M Veerappa
University of Mysore, India