Volume 24, Issue 2 (June & July 2021)                   J Arak Uni Med Sci 2021, 24(2): 168-179 | Back to browse issues page


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Asad Samani M, Peymani M. Changes in the Expression of SGO1 and SGO1-AS1 Genes in Colorectal Tumor Tissues, Compared to Healthy Tissues. J Arak Uni Med Sci 2021; 24 (2) :168-179
URL: http://jams.arakmu.ac.ir/article-1-6385-en.html
1- Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran.
2- Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran. , m.peymani@iaushk.ac.ir
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1. Introduction
olorectal cancer is among the leading causes of death and is the fourth most common cancer worldwide [1] that ranks third among women [5, 432]. The SGO1 protein is a member of the shugoshin protein family. Besides, and decreased expression of the SGO1 gene leads to the premature destruction of the centromere during mitosis [87 ,6]. Mutations in the SGO1 gene lead to transcriptomic changes in metabolism, proliferation, and immune responses in the gut that contribute to cancer progression [9]. lncRNAs play an important role in controlling cell growth by regulating the cell cycle and apoptosis [10]. Growth Arrest-Specific (GAS5) accumulates in stunted growth cells and sensitizes mammalian cells to apoptosis [11]. Regarding the role of SGO1-AS1 and subsequent tumorigenesis and regulation of SGO1 gene expression, in this study, for the first time, the expression of SGO1-AS1 and SGO1 genes in colorectal cancer tumor tissue was compared with healthy tissue.
2. Materials and Methods
The present case-control study was performed on 40 tumor tissues of 40 individuals with colorectal cancer and 40 adjacent healthy tissues. Trizol was used to extract total RNA and after qualitative and quantitative analysis, the cDNA of each sample was synthesized using the kit of Yekta Tajhiz Azma Company. Using the Real-Time-RT PCR technique and especially, designed reciprocating primers, a quantitative measurement of the expression level of the desired genes was performed. In this study, after obtaining the relative frequency of expression for SGO1 and SGO1-AS1 genes in colorectal cancer, different tests were implemented to compare the obtained data.
GraphPad Prism and Excel software were used to analyze the collected data; after confirming the normality of the sample size with the Shapiro test, a t-test was used to examine the difference in the expression of SGO1 S and SGO1-AS1 genes in tumorous and healthy samples. One-Way Analysis of Variance (ANOVA) was used to compare the expression of genes in different stages. Spearman test was also used to examine the correlation of expression of the desired genes. Finally, to evaluate the specificity and sensitivity of each gene, the ROC test was applied to plot the ROC Curve.
3. Results
As shown in Figure 1A, the expression level of SGO1 was significantly reduced in tumor samples, compared to healthy tissue (P<0.001). 

However, the expression level of SGO1-AS1 in tumor tissue presented a significant increase, compared to the healthy tissue (Figure 1B) (P=0.0116). The expression levels of SGO1 and SGO1-AS1 in different stages of the disease were analyzed in tumor tissues. The relevant results indicated that the expression level of these genes remained unchanged at different stages of the disease (Figures 1C & D).
The expression level of SGO1 in the age group under 60 years illustrated less expression; however, the expression level of SGO1-AS1 revealed a significant increase in this age group, compared to the age group over 60 years. Figures 2A and B demonstrate a graph of changes in the relative expression levels of genes at the Ct Δ -2 level in both age groups in tumor tissues. 

The results concerning the ROC curve diagram indicated that the marker SGO1-AS1 with the area below the surface of the diagram (AUC=0.6364 & CI=0.5069/7669) acted as a poor marker in the diagnosis of colorectal cancer (Figure 3A). 

However, SGO1, as a marker can significantly (P<0.0001) separate the patient population from the healthy groups; with the area below the surface of the chart (AUC=0.8041 & CI=0.7036/9045), it can be a good marker to help improve the diagnosis of colorectal cancer (Figure 3B).
4. Discussion and Conclusion
The present study data indicated that in the tumor tissues of colorectal cancer, the expression of the SGO1 gene decreases, and the expression of the SGO1 -AS1 gene increases, compared to healthy tissue. In other words, the SGO1 gene acts as a tumor suppressor and the SGO1-AS1 gene as an oncogene. In a 2006 study of the SGO1 gene, Yang et al. Stated that human SGO1 has become a good target for inducing apoptosis into transformed cells [15]. In 2015, Wang et al. examined the SGO1 gene in liver cancer. They stated that the SGO1 gene is a potential therapeutic target for liver cancer [19]. In 2018, Ong et al. reported that an increase in lncRNA expression is detected in individuals with colorectal cancer [20].
In 2019, Mu et al. argued that SGO1 expression levels were higher in PCA (prostate cancer) tissue and cell lines. There was a correlation between SGO1 expression and preoperative prostate-specific antigen (P=0.01). Furthermore, gene expression was significantly associated with lymph node metastasis (P=0.044) [21]. This study also revealed that SGO1 decreased expression in colorectal cancer tumor samples. Measuring SGO1-AS1 expression in tumor and healthy colorectal cancer samples also identified an increase in LncRNA expression; these two genes could be used as a marker for the diagnosis of colorectal cancer.

Ethical Considerations
Compliance with ethical guidelines

This study was approved by the Ethics Committee of Shahrekord Azad University (Code: IR.IAU.SHKREC.1398.020).

Funding
This study was extracted from the MSc. thesis of the first author at the Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran. Also, this study was supported by the Vice Chancellor for Research of Islamic Azad University, Shahrekord.

Authors' contributions
Both authors met standard writing standards based on recommendations from the International Committee of Medical Journal Publishers.

Conflicts of interest
The authors declared no conflicts of interest.


Refrences
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Type of Study: Original Atricle | Subject: Basic Sciences
Received: 2020/07/15 | Accepted: 2020/08/25

References
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2. Ansari R, Mahdavinia M, Sadjadi A, Nouraie M, Kamangar F, Bishehsari F, et al. Incidence and age distribution of colorectal cancer in Iran: results of a population-based cancer registry. Cancer lett. 2006;240(1):143-7. doi.org/10.1016/j.canlet.2005.09.004. [DOI:10.1016/j.canlet.2005.09.004]
3. Burt RW, Barthel JS, Dunn KB, David DS, Drelichman E, Ford JM, et al. Colorectal cancer screening. J NATL COMPR CANC NE. 2010;8(1):8-61. doi.org/10.6004/jnccn.2010.0003. [DOI:10.6004/jnccn.2010.0003]
4. Kumar V, Abbas AK, Aster JC. Robbins basic pathology e-book: Elsevier Health Sciences; 2017.
5. Pahlavan PS, Kanthan R. The epidemiology and clinical findings of colorectal cancer in Iran. J Gastrointest Liver. 2006;15(1):15.
6. Mahapatra K, Roy S. An insight into the folding and stability of Arabidopsis thaliana SOG1 transcription factor under salinity stress in vitro. Biochem Biophys Res Commun. 2019;515(4):531-7. doi.org/10.1016/j.bbrc.2019.05.183. [DOI:10.1016/j.bbrc.2019.05.183]
7. Piché J, Gosset N, Legault L-M, Pacis A, Oneglia A, Caron M, et al. Molecular signature of CAID syndrome: noncanonical roles of SGO1 in regulation of TGF-β signaling and epigenomics. CMGH Cell Mol Gastroenterol. 2019;7(2):411-31. doi.org/10.1016/j.jcmgh.2018.10.011. [DOI:10.1016/j.jcmgh.2018.10.011]
8. Mishra PK, Thapa KS, Chen P, Wang S, Hazbun TR, Basrai MA. Budding yeast CENP-ACse4 interacts with the N-terminus of SGO1 and regulates its association with centromeric chromatin. Cell Cycle. 2018;17(1):11-23. doi.org/10.1080/15384101.2017.1380129. [DOI:10.1080/15384101.2017.1380129]
9. Rao CV, Sanghera S, Zhang Y, Biddick L, Reddy A, Lightfoot S, et al. Systemic chromosome instability resulted in colonic transcriptomic changes in metabolic, proliferation, and stem cell regulators in SGO1−/+ Mice. Cancer res. 2016;76(3):630-42. doi: 10.1158/0008-5472.CAN-15-0940 Published February 2016. [DOI:10.1158/0008-5472.CAN-15-0940]
10. Ulitsky I, Bartel DP. lincRNAs: genomics, evolution, and mechanisms. Cell. 2013;154(1):26-46. doi.org/10.1016/j.cell.2013.06.020. [DOI:10.1016/j.cell.2013.06.020]
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12. Yao Y, Dai W. Shugoshins function as a guardian for chromosomal stability in nuclear division. Cell Cycle. 2012;11(14):2631-42. doi.org/10.4161/cc.20633. [DOI:10.4161/cc.20633]
13. Gooding AJ, Zhang B, Jahanbani FK, Gilmore HL, Chang JC, Valadkhan S, et al. The lncRNA BORG drives breast cancer metastasis and disease recurrence. Sci rep. 2017;7(1):1-18. doi.org/10.1038/s41598-017-12716-6. [DOI:10.1038/s41598-017-12716-6]
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18. Chen C, Tan R, Wong L, Fekete R, Halsey J. Quantitation of microRNAs by real-time RT-qPCR. PCR protocols: Springer; 2011. p. 113-34. doi.org/10.1007/978-1-60761-944-4_8. [DOI:10.1007/978-1-60761-944-4_8]
19. Wang L-H, Yen C-J, Li T-N, Elowe S, Wang W-C, Wang LH-C. SGO1 is a potential therapeutic target for hepatocellular carcinoma. Oncotarget. 2015;6(4):2023. doi: 10.18632/oncotarget.2764. [DOI:10.18632/oncotarget.2764]
20. Ong MS, Cai W, Tan TZ, Huang RY-J, Hooi SC, Yap CT, et al. Long non-coding RNA landscape in colorectal cancer. RNA & disease. 2019;6. doi: 10.14800/rd.1628. [DOI:10.14800/rd.1628]
21. Mu J, Fan L, Liu D, Zhu D. Overexpression of shugoshin1 predicts a poor prognosis for prostate cancer and promotes metastasis by affecting epithelial-mesenchymal transition. OncoTargets ther. 2019;121111. doi: 10.2147/OTT.S191157. [DOI:10.2147/OTT.S191157]

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