Author

Jasmine Omran

Abstract

Non-small cell lung cancer (NSCLC) is the most prevalent class of lung cancer and the most common cancer worldwide. NSCLC accounts for 85% of total lung cancer cases and leads to the most cancer-related deaths worldwide. Micro RNAs (miRNAs) and long non-coding RNAs (lncRNAs) are gene regulatory elements that play crucial roles in cancer biology such as cancer cell proliferation, apoptosis, and metastasis. Understanding the gene regulatory elements that influence cancer biology is critical for diagnostic and therapeutic purposes. A systems approach can help simulate interactions between these elements. In this study 110 microarray samples from NSCLC patients were analyzed by computational methods to identify differentially expressed genes in two tissue types: NSCLC and normal lung tissue. Identified differentially expressed genes were functionally clustered and annotated with their miRNA and lncRNA targets using miRTarBase and starBase, respectively. Regulatory networks were created to suggest an interplay between these miRNAs, lncRNAs, and differentially expressed genes. This approach led to the identification of 108 differentially expressed genes. Innumerable miRNAs target the differentially expressed genes but 66 miRNAs were identified by literature mining and strong evidence validation methods to identify miRNA and differentially expressed gene targets. The filtered miRNAs were also paired with seven of the most common NSCLC-associated lncRNAs. Based on the findings of this study and other computational studies in literature, connections of differentially expressed genes, miRNAs, and lncRNAs were suggested. TGFBR3 and HHIP, tumor suppressor genes, and CAV1, an oncogene, were functionally related to carcinogenesis and cancer cell metastasis, respectively and were related to cell signaling and extracellular matrix genes. This study suggests that MALAT1, PVT1, and GAS5 are lncRNAs that regulate gene expression via miRNA targeting. Since miRNAs, and lncRNAs are instrumental gene regulatory factors in determining NSCLC diagnosis and prognosis, these regulatory pathways can lead to novel approaches in cancer therapy. Therefore, these networks propose mechanisms of actions to further study miRNAs and lncRNAs suggesting a crosstalk between miRNAs, lncRNAs, and differentially expressed genes.

Department

Biotechnology Program

Degree Name

MS in Biotechnology

Date of Award

2-1-2016

Online Submission Date

January 2017

First Advisor

Azzazy, Hassan

Committee Member 1

Amleh, Asma

Committee Member 2

Aziz, Ramy

Document Type

Thesis

Extent

88 p.

Rights

The author retains all rights with regard to copyright. The author certifies that written permission from the owner(s) of third-party copyrighted matter included in the thesis, dissertation, paper, or record of study has been obtained. The author further certifies that IRB approval has been obtained for this thesis, or that IRB approval is not necessary for this thesis. Insofar as this thesis, dissertation, paper, or record of study is an educational record as defined in the Family Educational Rights and Privacy Act (FERPA) (20 USC 1232g), the author has granted consent to disclosure of it to anyone who requests a copy. The author has granted the American University in Cairo or its agents a non-exclusive license to archive this thesis, dissertation, paper, or record of study, and to make it accessible, in whole or in part, in all forms of media, now or hereafter known.

IRB

Not necessary for this item

Comments

First and foremost, I would like to thank my thesis advisor, Dr. Hassan Azzazy for all of his support. I would like to thank him as he helped me grow not only as a student but also as a scientist and a teacher. He continues to inspire me with his devotion to students and immense scientific knowledge. He is a role model for hard work and scientific innovations. Next, I would like to thank all my professors in the AUC Biotechnology program for contributing to the honing of my scientific knowledge. Also, I would like to thank Ahmed Elhosseiny for his support, bioinformatics help, and late hours. He is an icon of hard work and resilience. Also, I would like to extend many thanks to Marwa Zahra as she is supportive and provided her time, guidance, and intelligence. Last but not least, I would like to extend my gratitude to my mother and my friends for believing in me and for their continuous support.

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