Investigating POPDC Proteins as a Target in Multiple Cancers

This thesis investigates the role of Popeye domain-containing (POPDC) proteins, particularly POPDC1, POPDC2, and POPDC3, in the development and spread of various cancers. It examines the structure, function, and role of POPDC proteins in cancers such as breast, gastric, hepatocellular, colorectal, brain, esophageal, eye, and lung cancer. The research methodology involves analyzing existing articles, focusing on the role of POPDC1 in different cancers, and utilizing PubMed search techniques. Findings include comparisons of different cancers and strategies for prevention and treatment, such as Micro RNA, methyl light array, QPCR, and Array Screens. Recommendations include treatment options like photodynamic therapy, laser treatment, and hyperthermia, as well as lifestyle changes and drugs like Taxol, Antifabitin, and Doxacetol. The study concludes by summarizing the key findings and discussing the potential of POPDC proteins as drug targets in cancer treatment.

IS A POTENTIAL TARGET IN MULTIPLE CANCERS?
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Declaration
I, …………………………………………………………………………………………….
[please print name] hereby declare that all the works in this dissertation is my own except for
quotations and Abstract that have been duly acknowledged. This report has not been accepted
for any degree and has not been submitted for any award of any other degrees. The work
presented in it is my own and has generated as a result of my own research.
‘Is a potential target in multiple cancers?’
………………………………………………………………………………………………
I confirm that:
1. This work was totally done or mainly during candidature for a research degree at this
University;
2. A clear statement has been made at that part where this dissertation had not submitted
previously for a degree or rest qualification in any other institutions;
3. A clear attribution has been consulted to publish work of others;
4. The sources have been mentioned from where I have quotes the other’s works. Along
with the exception of this quotations the whole dissertations has been made by myself;
5. All the sources I have used are acknowledged and relevant;
Signature: …………………………………………………………………………
ID Number:..............................................................................................................
Date:.........................................................................................................................
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Abstract
The study has provided a comprehensive understanding of the POPDC protein that belongs to
the cAMP effector protein. The study has demonstrated the structures, compositions, and
roles of different protein genes (POPDC1, POPDC2, and POPDC3) that are differently
responsible for the generation of different categories of cancer. The paper includes the
research aim, objectives, and questions that are achieved by conducting this research. This
assignment has included the process of spread of cancer cells due to the presence of the
POPDC proteins. The POPDC protein stimulates the cell division and migration that rapidly
increases the rate of spread of the cancer cells. The POPDC protein is responsible for cancer
in the brain, lungs, skin, breast, stomach, Colin and other the body parts of the human body.
The dissertation includes the functions, structures, and composition of the POPDC protein.
The roles of the different genes of the POPDC protein on the generation of different cancers
are included with the paper. The paper also contains the conclusions and recommendations
regarding the reduction of the cancer-causing POPDC protein.
In the methodology section, the different methods and materials that are used in this study are
analyzing various articles and providing evidence. In this study, the different methods that
can be used for data collection are Cell lines, samples of tissues conducting various tests and
the immunochemistry.
In section Findings and analysis the different strategies that can be used for prevention of
cancer are explained. The most common type of strategy that can be used for therapeutic
intervention of cancer is Micro RNA. Another strategy that can be used for the detection of
cancer is methyl light array, QPCR and Array Screens.
In the recommendation section, the different treatment options are explained such as
Photodynamic therapy, laser treatment, and Hyperthermia. Moreover, in this section the
different types of strategies are also explained for prevention of cancer such as consumption
of a healthy diet, indulging in physical activity and others. Moreover, in this, the drugs that
can help in prevention and treatment of cancer are also explained such as Taxol, Antifabitin
and Doxacetol.
In the conclusion section, the summary of the study is explained. In this section, the key
finding of the study is discussed. Moreover, in this section, the role of POPD in different
cancers is explained. Moreover, in this section, a brief of the whole study is provided.
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Table of Contents
1. Introduction.........................................................................................................................7
1.1 Function of POPDC.....................................................................................................7
1.2 Structure of POPDC.........................................................................................................7
1.2 Role of POPDC...........................................................................................................9
1.3 Research Aim..............................................................................................................9
1.4 Research Objectives....................................................................................................9
1.5 Research Questions.........................................................................................................10
2.0 Research Methodology.......................................................................................................10
3.0 Discussion..........................................................................................................................12
3.1 Different types of POPDC protein.................................................................................12
3.2 Comparison of POPDC1, POPDC2 and POPDC 3........................................................12
3.3 Role of POPDC in breast cancer....................................................................................13
3.4 Role of POPDC in gastric cancer...................................................................................14
3.5 Role of POPDC in hepatocellular carcinoma.................................................................15
3.6 Role of POPDC in colorectal cancers........................................................................16
3.7 Role of POPDC in brain cancer...................................................................................17
3.8 Role of POPDC in esophageal cancer............................................................................18
3.9 Role of POPDC in Eye neoplasm...................................................................................18
3.10 Role of POPDC in other cancers..................................................................................19
3.11 Role of POPDC on lung cancer....................................................................................19
4.0 Findings and Results..........................................................................................................20
4.1Comparing and Contrasting of different cancers.............................................................20
4.2 Strategies related to different Cancer.............................................................................25
5. Recommendation..................................................................................................................30
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7. Conclusion........................................................................................................................31
Reference list............................................................................................................................34
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Acknowledgement
For overseeing this course in order to investigate, I will need an adequate measurement of
thankfulness to my educational director ________________. Besides that, I want to show
gratefulness to my educator ………….. Who helped me throughout this dissertation work. I
would like to thank my friends, my tutors, my institutional lecturers. In a mannerly way
regarding my appreciation from my beginning to finish it accomplishes for seasonal
conferring in order to gather the data. Before I finish, I have to show the appreciation to all of
my managers and the employees of my institution……………………………..those have
played an enthusiastic roles for data accumulating methods. Without their shoring off, there a
presumably happens that would endeavour and complete. For a successful submitting, I
would like to dedicate a sincere appreciation to my
supervisors………………………………………………………………………….at
…………………………………………………………………………………….(Name of the
University) for allowing me to do this dissertation under their supervision. All of them have
provided me the encouragement, critics, guidance, valuable guidance in order to finish this
project. Without their constant support this project would not have been as same as the
presentation. My classmates is deserved to be recognized for their friendship and supporting.
Warm thanks also goes towards those who have provided me the assistance at numerous
situations that also invite either directly or indirectly in the complex of my project. Finally,
but certainly not in least, my acknowledgement also extends to my family for continuing
supporting and encouragement.
Thanking You.
Yours Sincerely,
…………………………………………………………………………………
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1. Introduction
The Popeye domain containing (POPDC) proteins are considered as the novel class of the
category of cAMP effectors proteins (Brand, et al., 2014). This protein family could be
found in the muscular cells (Amunjela, and Tucker, 2016). The three members of POPDC
protein (POPDC1, POPDC2, and POPDC 3) are responsible for the development, spread
and migration of the cancer cells. The medical science has explored that the POPDC
group of protein is accountable for the different category of cancers like breast cancer,
gastric cancer, oesophageal cancer, liver and stomach cancer, lung cancer and ovarian
cancer.
Function of POPDC
The main functional area of POPDC protein is the striated muscle. This protein plays a
vital role in the activity of controlling the distribution of macromolecules throughout the
body cells (membrane trafficking). The POPDC is responsible to control the interacting
protein bodes. As per the recent researches, the POPDC proteins could also control the
level of the cells of nuclear proto-oncogene protein named c-Myc (Han et al. 2014)
Figure 1.1: POPDC
(Source: Schindler, and Brand, 2016)
1.2 Structure of POPDC
Analyzing the POPDC protein, the following structure could be derived:
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 The POPDC protein is composed of three integral membrane proteins (also
known as transmembrane protein) that have short amino terminus situated in
the extracellular space in the cortex (extracellular) containing two numbers of
N- Glycosylation sites.
 Inthe case of the POPDC protein, the rate of Glycosylation is very high; hence
this stimulates the electrophoretic mobility in the sodium dodecyl sulfate
(SDS).
 The rate of Glycosylation, as well as the electrophoretic mobility in the
sodium dodecyl sulfate (SDS) PAGE, is dependent on the tissues.
 The localization of the membrane of the POPDC protein is controlled by
glycosylation.
 The glycosylation is present in the POPDC protein that protects this protein
from the breakdown into smaller polypeptides.
 The C-terminus of this protein is a composition of the Popeye domain (PFAM:
PF04831) that includes near about 150 amino acids.
 The POPDC protein has a similar structure as the other four cAMP binding
domains.
 POPDC protein is enriched with the amino acids and C4H9NO3 that are
responsible for the chemical addition of PO3- group in the cells (the process is
also known as phosphorylation).
Figure 1.2: Structure of POPDC
(Source: Amunjela, and Tucker, 2017)
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Role of POPDC
The POPDC protein has a significant role in the human body, such as:
 The POPDC protein stimulates the cell division and assists in the process of
spreading of cancer (Han et al., 2019).
 This protein is responsible for the diminishing of muscles in the limbs, arms,
and legs. The wastage of muscle causes weakness of the body. Hence, POPDC
protein is accountable for the muscular dystrophy of limbs.
 POPDC proteins are responsible for the development and spread of heart
disease Rossi (Rossi, 2017). The heart disease caused due to the POPDC
protein is known as cardiac arrhythmia.
 POPDC proteins damage the conduction between ventricles and atria of the
heart and cause heart blockage, which is known as Atrioventricular block in
medical science.
 This protein is also responsible for cancer of other body parts like breasts,
stomach, liver, ovary, and lungs.
Research Aim
The research aims to discover, identify, and analyze the role of POPDC proteins (the
three genes POPDC 1, POPDC 2, and POPDC 3) on the development and spread of
different categories of cancer. This will be the focus of this research to explore the pattern
or distribution of the same.
Research Objectives
The research is conducted with the following objectives:
 To analyze the role of POPDC protein in the development and spread of
different categories of cancer
 To understand the difference between the different types of cancer as well as
the POPDC genes
 To review the molecular targeting of the POPDC2 gene (popeye domain)
 To analyze the viability of POPDC as a drug target in the area of cancer
treatment
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 To be able to recommend which sort of drugs could be used in the upcoming
future to reduce the rate of growth of POPDC proteins in order to control
cancer
1.5 Research Questions
2. What is the difference between the three genes of POPDC protein?
3. What is the difference between different categories of cancers (lung cancer, breast
cancer, gastric cancer, colorectal cancer, and hepatocellular cancer)?
4. What is the role and function of POPDC protein in the different types of cancers?
5. What is the feasibility of POPDC protein as a drug target in the area of cancer
treatment?
6. What sort of rugs could be used to control the action of POPDC protein over cancers?
2.0 Research Methodology
The research methodology used in this study includes finding articles using pub med sources.
The methodology includes searching articles using heading that is POPDC in Cancer. Then
the scope and content of the Pubmed articles are understood. In this study, the different
articles are searched based on the POPDC1 in each cancer and explain the methods include in
these articles. The different ways in which the articles are searched using PubMed are
Boolean operators in which the articles are always used in the uppercase. AND is used for
searching articles that include all the terms whereas NOT is used to exclude the search
criteria In this study, the terms that were included in this article include POPDC1 in cancer
and not included terms such as POPDC2, POPDC 3 in cancer. Another method that is used
for making search in PubMed is Truncation in which the terms are replaced by many
characters at the end of the search term. In this study, the different terms that are to be
truncated are found to be POPDC, Cancer, BVES, POPDC 2 and POPDC3. The other tools
that can b used in Pubmed for making better research is Single Citation Matcher which can be
used for accessing the full text of the reference required. The other tool that is commonly
used in PubMed is the MeSH Database in which the name of the search criteria is entered
automatic translation takes place thereby helping the researcher in categorizing the topics in
to different headings and sub headings. In this study, when the researcher entered the
POPDC1 in cancer no search results were found. However, when the search was broaden and
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the terms given in MeSH database that is Popeye domain containing proteins nearly 11
results were found.
The researcher Han et al. (2019) explains the different level of POPDC 1 in different cancers
such as in Lung, gastric, colorectal, haptelluar carcinoma, breast and eye cancer. The
researcher Han et al. (2019), the POPDC 1 level that is nor explained for different cancers
include in liver cancer. On the other hand, Ordeanu et al. (2015), included patients that have
undergone squamous carcinoma cell whereas excluded those patients that have undergone
Brach therapy. The researcher conducted a quantitative research approach that is the
researcher conducted the test of nearly 26 patient and the researcher intend to identify the
different stages in which patient belongs. In this study, it was found that the nearly 57% of
patients were found to be 57% of patient were suffering from cervical cancer at stage III,
nearly 23% of people are suffering from cervical cancer at Stage III A and nearly 11% of
people are suffering from cervical cancer in III B disease. As explained by Schindler et al.
(2016), in this methodology, 104 patients were screened with various clinical features such as
block, arrythamtic and sudden death. As explained by Ashokan et al. (2018), Data related to
RNA Genes was collected from 153 patients were collected as samples. The average tumor
sample was found to be 2.98 which were found to be lower than the normal level.
The researchers Kim, Yoo and Kim (2010), established nearly 11 cell lines that were
suffering from gastric cancer obtained from Cell Line Bank. It was found that nearly 73%
was found to be down-regulated in tumors and normal tissues. On the other hand, the
researcher Luo et al. (2012), investigated the expression of POPDC in nearly 306 human
cases that were suffering from gastric cancer and 84 patients that did not consist of gastric
tissues. The result includes low expression of POPDC 3 in humans that can cause the
progression of cancer that is gastric. This can be proved by the results founded in this study
that is that high expression of POPDC was found in nearly 25% of patients whereas low
POPDC expression was found in 74% (Luo et al., 2012). Moreover, the researcher also found
that the survival rate of a patient with low POPDC expression was lower as compared to
people with high POPDC expression. The people with low POPDC expression had a survival
rate of 73% - 16% whereas people with High POPDC expression have a high survival rate
that is near to 88% (Luo et al., 2012). On the other hand, Williams et al. (2011), the results
found include that 0.5% of people are found to have low expression of POPDC thereby
helping in better analysis of the presence of POPDC in the patients that are suffering from
cancer.
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3.0 Discussion
3.1 Different types of POPDC protein
There are three genes POPDC 1, POPDC 2, and POPDC3 present in the POPDC gene family.
All three genes are generated due to the evolution of the POPDC gene family. The numbers
of POPDC genes are not equal in all the spices. In case of the lower chordates species, there
are two numbers of POPDC genes. In the case of the vertebrates, all three genes of POPDC
are found.
Figure 3.1: Evaluation of POPDC gene
(Source: Brand, 2015)
3.2 Comparison of POPDC1, POPDC2 and POPDC 3
Basis of comparison POPDC 1 POPDC2 POPDC3
Location In the human body,
this is located on
chromosome 6q21
In the human body,
this is located on
chromosome
In the human body,
this is located on
chromosome 6q21
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