Identification of
the effect of lycopene on the inhibition of yellow fever-causing flavivirus by
studying microarray gene expression data
1
Cellular
and Molecular Biology, Faculty of Natural Sciences, University of Tabriz,
Tabriz, Iran
*Corresponding
Author: Gholamreza Dadashi Oranj
* Email: Angoot63@yahoo.com
Abstract
Introduction: Yellow fever virus causes systemic disease of the liver, kidneys,
myocardium and hemorrhage, which are high incidence and mortality. Lycopene is
one of the effective antioxidants used to prevent the growth of cancerous
tumors. DNAJC14 protein is a variant of heat shock protein (chaperone) Hsp40.
Hsp40 chaperone protein (DNAJC14) that when overexpressed was able to mediate
protection from yellow fever virus (YFV)-induced cell death. In this study, to
find a new treatment for yellow fever, the effect of lycopene on the expression
of DNAJC14 gene involved in yellow fever was investigated.
Materials
and Methods: In this project, using bioinformatics software, such as Matlab and
Cytoscape, the effect of lycopene on the expression of DNAJC14 gene, as well as
the relationship of this gene with different genes have been investigated. Big
gene expression data in the NCBI database were used for this study.
Results: Analysis of microarray data showed that the expression level of
DNAJC14 gene was increased under the influence of lycopene.
Conclusion: The lycopene combination can be used as a preventative and even
treatment for yellow fever viral disease due to the effect DNAJC14 gene
expression.
Keywords: Lycopene, Yellow fever, Bioinformatics, Co- expression, Microarray, Cytoscape
Introduction
Flaviviruses
of the Flaviviridae family are transmitted through arthropods and contribute to
the astonishing number of significant human infections and deaths worldwide
each year (1). Heat shock proteins are a family of highly conserved
evolutionary proteins expressed in eukaryotes and prokaryotes. The expression
of HSPs is increased in various cellular stresses, including heat stress, which
occurs in the host organism as well as in pathogens in response to infection
and inflammation (2). The DNAJC14 gene, which is a member of the Hsp40 family
of chaperones, can inhibit the proliferation of flaviviruses (3). Overexpressed
DNAJC14 is targeted to sites of yellow fever virus (YFV) replication complex
(RC) formation, where it interacts with viral nonstructural (NS) proteins and
inhibits viral RNA replication (4). Lycopene is a natural carotenoid and
pigment that is made by plants and microorganisms to absorb light during
photosynthesis. Vegetables and fruits that have a red color are important
sources of lycopene, including tomatoes, watermelon, grapefruit, etc (5). In
this study, to find a new, cheap and convenient method for the treatment of
yellow fever, the effect of lycopene on the expression of DNAJC14 gene involved
in yellow fever was investigated. Microarray has been one of the most widely
used methods of generating Big data related to gene expression in genome
performance projects. GEO (Gene Expression Omnibus) is one of the best repositories
for gene expression databases located in the NCBI. Available microarray data
includes raw data. Numerous software and hardware have been designed to use
this data. Therefore, in proportion to the purpose of this research, these raw
data have been used. In this study, we used the microarray data of a research
project with access number 27140 (6). In the mentioned project, gene expression
data of thousands of genes under the influence of lycopene were extracted as
raw data and recorded in GEO. We analyzed the expression of DNAJC14 gene, which
plays a key role in yellow fever, among a large number of genes and big data
sets, and showed the results in the form of clustergram and histogram.
Materials and Methods
To
receive gene expression data due to the effect of lycopene on DNAJC14 has been
referred to the NCBI site. In the microarray project with access number
GSE27140, the effect of lycopene consumption on gene expression in prostate
cancer patients has been recorded as raw data on the NCBI section of GEO
section. The GSE27140 project is a 2003 study of changes in the cox-2 and IGF-1
genes in patient with prostate cancer who were treated with lycopene (6). In
the mentioned project, the expression of thousands of genes has been extracted
and recorded in the form of raw data. We extract the DNAJC14 gene expression
data by giving its special identification code (AA461486) from the data set
which is registered as a matrix series on the NCBI website and import it into
an Excel file. To get the p-value of analysis referred to GEO2R section at NCBI
(Table 1). As described in GSE27140 research, gene expression data were
obtained from microarray of prostate tissue biopsy in patients with prostate
cancer. These patients underwent biopsy on the first day of the project and on
the 90th day after treatment (6). By importing the given files in Excel format
in MATLAB software and executing Syntax codes in MATLAB software, clustersgram
(Figure 1) and histograms (Figure 2A & 2B) of DNAJC14 gene expression were
extracted and displayed. And finally, we have used cytoscape software to
demonstrate DNAJC14 co-expression with other genes (Figure 3).
Results
In Table 1, we have extracted and demonstrated the p-value of the
gene analysis with its special code and symbol (p-vlue=0/000963). In the GEO
dataset, the DNAJC14 gene is codenamed AA461486.
Table 1. DNAJC14 gene identification
code and p-value.
|
ID |
Adj.P.val |
P.value |
t |
Logfc |
Gene symbole |
|
AA461486 |
0.2064 |
0.000963 |
-3.46 |
0.716 |
DNAJC14 |
After receiving the raw data related to the DNAJC14 gene from GEO
dataset, we entered the data file as an excel file into the Matlab software,
and by executing command codes to compare the expression of the desired gene on
day 0 and day 90 after lycopene consumption, The result shown as a clustergram.
As it has been shown, the expression of this gene shows an increase compared to
day zero (start of the study) (Figure 1).
Figure 1. In this clustergram, 29 patients
each have two samples of gene expression on day 0 and day 90 of the project.
Horizontal odd numbers are gene expression on day 0 and horizontal even numbers
are gene expression on day 90 of the project. Light green indicates the least
and light red indicates the most expression.
In another
method, using MATLAB software, the analysis result is shown as a histogram.
Each bar is related to gene expression at day zero and day 90 after lycopene
use. Gene expression has been shown to increase after 90 days of lycopene use
(Figure 2A & 2B). Comparison of
histograms on day zero and day 90 showed increased DNAJC14 gene expression.
Figure 2A . The DNAJC14
gene expression histogram on day zero of the project, which is the range of
gene expression between zero and minus 12.
Figure 2B. The DNAJC14
gene expression histogram on day 90 of the project has a range of gene
expressions ranging from an approximately negative one to positive ten.
Also, the relationship between DNAJC14 gene and other genes has
been shown in terms of expression, using Cytoscope software) Figure 3(. According to the results of the analysis
by Cytoscope software, different genes are co-expressed with DNAJC14 gene. Blue
rectangles show related genes that are connected to DNAJC14 gene by bridges.
Figure 3. Co-Expression of DNAJC14 gene with other genes, in this form,
genes that are linked to the DNAJC14 gene in terms of expression bind to the
gene with the bridges.
Discussion
The
causative agent of yellow fever is a virus (7). Vaccines are used to prevent (8)
and Ribavarin drug is used to treat the disease (9). Vaccines are also used to
increase the body's resistance and immunity against this virus (10). The
compound studied in this study is lycopene, which is used to prevent the growth
of cancerous tumors (5). HSPs are a family of highly conserved evolutionary
proteins that are expressed in eukaryotic and prokaryotic organisms. In people
who have a mutation in this gene and the gene has been turned off, the rate of
virus replication is high, and disease and death are similarly high (3).
DNAJC14 is an Hsp40 family member that broadly modulates flavivirus replication
(11). This study found that lycopene significantly increased DNAJC14 gene
expression. Comparing scientific documents, it was found that lycopene
increases the level of DNAJC14 protein in cells by increasing the expression of
a key gene involved in yellow fever, thus preventing the proliferation of
disease-causing viruses. Taking a combination of lycopene is one of the
simplest and easiest ways to increase the body's immunity against flaviviruses.
By consuming and using foods containing this compound and even capsules and
pills of this effective substance, yellow fever can be prevented rather, it
treated yellow fever by consuming this nutrient and increasing the inductive
expression of DNAJC14 gene through the use of lycopene. Due to the fact that
the microarray data used in this study was obtained from a prostate biopsy in
the study with the access number GSE27140 (6). Therefore, it is suggested that
another study be performed by PCR method of biopsy of liver tissue of
individuals and the result of the study be compared with the result of the
present study.
Conclusions
This study showed that the lycopene, a carotenoid compound with
antioxidant properties, has an additive effect on the expression of DNAJC14
gene. DNAJC14 protein belongs to the group of chaperones and prevents the
proliferation of flaviviruses that cause yellow fever. As a result, the
consumption of lycopene in fruits and vegetables such as tomatoes, carrots and
cabbage can increase the immunity of the body cells by increasing the
expression of DNAJC14 protein against flaviviruses and yellow fever. And also
help in the treatment of this disease if it is contracted. According to the results of this study, we
can use lycopene as a low-cost and convenient treatment for yellow fever.
Conflict of interest
The
authors declare that they have no conflicts of interest.
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