عنوان

miRNA profiling in IRAQI patients with gastric cancer

شماره

T28875

زبان متن نوشتاري يا گفتاري و مانند آن

انگلیسی

عنوان اصلي

miRNA profiling in IRAQI patients with gastric cancer

نام عام مواد

Dissertation

نام نخستين پديدآور

Mohanad Al-Khalidi

نام ناشر، پخش کننده و غيره

Natural Sciences

تاریخ نشرو بخش و غیره

1402

نام خاص و کميت اثر

125p.

ساير جزييات

cd

جزئيات پايان نامه و نوع درجه آن

Ph.D.

نظم درجات

Molecular Genetics

زمان اعطا مدرک

1402/04/07

متن يادداشت

The fifth leading cause of cancer in the world is gastric cancer (GC). Currently, the usual treatment for this aggressive disease consists of surgery and systemic chemotherapy. The development of gastric cancer is a highly complex process in which the proliferation, migration and invasion of cancer cells play essential regulatory roles. Due to the lack of observable symptoms of gastric cancer, gastroscopy is still the gold standard for diagnosing the disease, which has a high rate of false-negative results. Therefore, the establishment of effective biomarkers technology for detecting gastric cancer would significantly lower the overall mortality rate.This work intends to find differentially expressed microRNAs (miRNAs) in gastric cancer as well as evaluate the potential roles by comparing gastric cancerous tissues with marginally normal tissues. In addition to evaluation of the regulatory function of miR-221-3p in regulating PIK3R1 expression, as well as the invasion, migration, and proliferation of gastric cancer cells. To achieve this goal, a case control study has been conducted using 50 patients with 2 samples for each patient, including50 tumor and 50 non-tumor marginal tissue samples.Matched gastric cancer tissues, along with marginal normal tissues from 50 Iraqi patients following radical surgery was used to explore miRNA expression by microarray. A qRT-PCR was utilized to validate the findings of the microarray. The data showed that ~1365 displayed positive values in all tissue samples, among these miRNAs, 37 miRNAs were presented significant upregulation, and 40 miRNAs were presented significant downregulation when the cut-off point of average fold-change setting as ≥2-fold (Up-regulated) or <0.5 (Down-regulated) and p value <0.05. Then, a qRT-PCR was used to confirm the findings of the microarray results by choosing 3 candidate miRNAs, including (miR-221-3p, miR-21-5p, and miR-106a-5p) and the expression of these miRNAs, as determined by real-time RT-PCR in the same samples, was consistent with that determined by miRNA microarray screening. Also, these miRNAs had shared with 1414 target gene intersections. Additionally, KEGG Pathway enrichment analysis and Gene Ontology (GO) analysis were carried out for the potential miRNAs and showed that the GO analyses for these 3 miRNAs may be contribute to a variety of processes including stem cell differentiation, cell-cell junction and GTPase binding. On the other hand, KEGG pathway analyses indicated that the candidate miRNAs were significantly participated in different KEGG signaling pathways which include pathways in cancer, gastric cancer, and other oncogenic/tumor suppressor transduction systems such as PI3K-Akt signaling pathway and p53 signaling pathway.We additionally examined the function of miR-221-3p in GC cells through proliferation, migration and invasion tests by miRNA mimic/inhibitor modulation in MKN-45 GC cells. Migration and proliferation of gastric cancer cells are critical factors affecting effective treatment. The results showed that overexpression of miR-221-3p leads to a significant increasing of proliferation, migration and invasion potency of MKN-45 cells along with weakened in PIK3R1 level (p<0.05) in the mimic group, while group transfected with miR-221-3p inhibitor exhibited a significant elevated in PIK3R1 expression with reducing in the proliferative, migratory and invasive activity of MKN-45 cells (p<0.05). According to bioinformatics analysis, A PIK3R1 target was identified as potential biomarker for the progression of GC. Moreover, knockdown of miR-221-3p with anti-miRNAs increased the PIK3R1 expression in GC cells. Functionally, miR-221-3p can suppress PIK3R1. In conclusion, data suggest that miR-221-3p can influence the formation of the GC by regulating the expression of this crucial gene.In this work, most gastric tumors have higher miR-221-3p expression than matching marginal normal tissues in addition to cancer cell and this provide evidence that miR-221-3p played an oncogenic role during gastric cancer pathogenesis via negatively regulation of PIK3R1 gene expression. The findings of this study point to the involvement of miR-221-3p in regulating the behavior of gastric cancer cells, however the subtype-specific expression patterns of miR-221-3p may represent different cell events or behaviors. These alterations could be the result of several miR-221-3p- regulated molecular signaling pathways. According to this study, the expression of miR- 221-3p specifically could be utilized as a biomarker to identify patients with gastric cancer and having higher malignant potential.Overall, the profile of differentially expressed miRNAs was successfully screened and our findings demonstrate that microRNAs are dysregulated in GC, indicating that these genes may be involved in both the development and progression of GC.

عنوان گونه گون

مشخصات بيان miRNA در بيماران عراقى مبتلا به سرطان معده

اصطلاح موضوعی

فاقد کلید واژه لاتین و فارسی

عنصر شناسه اي

Al-Khalidi,

ساير عناصر نام

Mohanad

کد نقش

Producer

عنصر شناسه اي

Safaralizadeh,

عنصر شناسه اي

Khalaj-Kondori,

عنصر شناسه اي

Latifi-Navid,

ساير عناصر نام

Reza

ساير عناصر نام

Mohammad

ساير عناصر نام

Saeid

کد نقش

Thesis advisor

کد نقش

Thesis advisor

کد نقش

Consulting advisor

عنصر شناسه اي

Tabriz

کشور

ایران

سازمان

CEntral Library of Tabriz University

شماره بازیابی

دکتری پایاننامه QL351.K4 1402

نام الکترونيکي

Mohanad Al-Khalidi

ارتباط براي تسهيلات دسترسي

عبادی

فرمت انتشار

e

نوع ماده

TL

کد کاربرگه

276903

سطح دسترسي

a

تكميل شده

Y