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Gene Reports
journal homepage: www.elsevier.com/locate/genrep
Identification of genes and miRNAs associated with angiogenesis,
metastasis, and apoptosis in colorectal cancer
Ramin Pourakbari
a,b
, Mohammad Hossein Mousavishenas
a
, Amin Kamrani
a
, Sanam Dolati
c
,
Hossein Abbaszadeh
a
, Majid Zamani
a
, Yoda Yaghoubi
a
, Shahriar Hashemzadeh
d
,
Majid Ahmadi
a,e
, Mohammad Hojjat-Farsangi
f
, Amir Mehdizadeh
g
, Mehdi Yousefi
e,h,
⁎
a
Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
b
Student's Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
c
Aging Research Institute, Tabriz University of Medical Sciences Tabriz, Iran
d
Department of General and Thoracic Surgery, Tabriz University of Medical Sciences, Tabriz, Iran
e
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
f
Department of Oncology-Pathology, Immune and Gene therapy Lab, Cancer Center Karolinska (CCK), Karolinska University Hospital Solna and Karolinska Institute,
Stockholm, Sweden
g
Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
h
Department of Immunology, Tabriz University of Medical Sciences, Tabriz, Iran
ARTICLE INFO
Keywords:
Colorectal cancer
Metastasis
Angiogenesis
Apoptosis
MicroRNAs
ABSTRACT
Colorectal cancer (CRC) is the main cause of cancer-related mortalities, worldwide and is the most prevalent
cancer of the gastrointestinal tract. Different techniques exist to diagnose CRC including colonoscopy, sigmoi-
doscopy, and plasma miRNA test. This study evaluates the important miRNAs and main genes playing role in
metastasis, angiogenesis and apoptosis that can be considered as prognostic and progression markers of CRC. We
have measured the expression levels of the miRNAs, and multiple genes related to angiogenesis, metastasis and
apoptosis in 45 paired samples of CRC tissue specimens and adjacent normal mucosa tissues obtained from 45
patients with CRC utilizing Real-time PCR. We have also analyzed the relationship between the expression of
these genes and clinic pathological features. Results showed that the expression levels of angiogenesis genes
(PGE-2, VEGF, Vimentin, CD105, CXCL-1, and IGFBP-7), metastatic genes (IGF-1R, Snail-1, and MMP-7) and
apoptotic genes (Bcl-2, Bcl-xl, and NF-κβ1) were significantly higher in cancer tissues. But the expression levels
of E-cadherin, AdipoR1, Claudin-7, Bax, Puma, and Noxa, were notably lower in cancer tissues. Additionally, it
was revealed that miRNAs (miR-21, miR-19a, miR-18a, and miR-92a) expression levels were in higher levels in
cancer tissues when compared to the normal tissues. In contrast, the expression levels of miR-31, and miR-139-
5p were significantly lower in cancer tissues. It is hoped that, by measuring the metastasis, angiogenesis and
apoptosis resistance associated miRNAs expression, better treatment results would be achieved in CRC treat-
ment.
1. Introduction
Colorectal cancer (CRC) is one of the main global health concerns
for its widespread morbidity and mortality (Sadreddini et al., 2017).
CRC is the third prevalent male gender malignancy and the second most
prevalent female cancer, worldwide (Tariq and Ghias, 2016). Annually,
1.2 million new cases of CRC are reported and 600,000 individuals die
from this cancer. The highest outbreak rate has been reported in
Oceania and Europe with the diagnosed average age of 65 years in
advanced countries (Brenner et al., 2014). Usually, this cancer is re-
sulted from the accumulation of epigenetic variations and genetic
mutations in colon epithelial cells that lead to the adenocarcinoma
https://doi.org/10.1016/j.genrep.2019.100552
Received 29 June 2019; Received in revised form 7 September 2019; Accepted 1 November 2019
Abbreviations: PGE-2, Prostaglandin E2; VEGF, vascular endothelial growth factor; CXCL-1, chemokine (C-X-C motif) ligand 1; IGFBP-7, Insulin-like Growth Factor
(IGF)-binding protein; AdipoR1, adiponectin receptor protein 1; IGF-1R, Insulin-like Growth Factor 1 receptor; MMP-7, matrix metalloproteinase-7; EMT, Epithelial
to Mesenchymal Transition; LDH, Lactate Dehydrogenase; ALP, Alkaline Phosphatase; CEA, Carcinoembryonic Antigen; MAPK, mitogen-activated protein kinase;
EGFR, epidermal growth factor receptor
⁎
Corresponding author at: Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
E-mail address: Yousefime@tbzmed.ac.ir (M. Yousefi).
Gene Reports 18 (2020) 100552
Available online 06 November 2019
2452-0144/ © 2019 Elsevier Inc. All rights reserved.
T