Integrated whole transcriptome and small RNA analysis revealed multiple regulatory networks in colorectal cancer

Shaath, H; Toor, SM; Nada, MA; Elkord, E; Alajez, NM

Abstract

Colorectal cancer (CRC) remains a global disease burden and a leading cause of cancer related deaths worldwide. The identification of aberrantly expressed messenger RNA (mRNA), long non-coding RNA (lncRNA), and microRNA (miRNA), and the resulting molecular interactions and signaling networks is essential for better understanding of CRC, identification of novel diagnostic biomarkers and potential development of therapeutic interventions. Herein, we performed microRNA (miRNA) sequencing on fifteen CRC and their non-tumor adjacent tissues and whole transcriptome RNA-Seq on six paired samples from the same cohort and identified alterations in miRNA, mRNA, and lncRNA expression. Computational analyses using Ingenuity Pathway Analysis (IPA) identified multiple activated signaling networks in CRC, including ERBB2, RABL6, FOXM1, and NFKB networks, while functional annotation highlighted activation of cell proliferation and migration as the hallmark of CRC. IPA in combination with in silico prediction algorithms and experimentally validated databases gave insight into the complex associations and interactions between downregulated miRNAs and upregulated mRNAs in CRC and vice versa. Additionally, potential interaction between differentially expressed lncRNAs such as H19, SNHG5, and GATA2-AS1 with multiple miRNAs has been revealed. Taken together, our data provides thorough analysis of dysregulated protein-coding and non-coding RNAs in CRC highlighting numerous associations and regulatory networks thus providing better understanding of CRC.

Citation

Shaath, H., Toor, S., Nada, M., Elkord, E., & Alajez, N. (2021). Integrated whole transcriptome and small RNA analysis revealed multiple regulatory networks in colorectal cancer. Scientific reports, 11(1), 14456. https://doi.org/10.1038/s41598-021-93531-y

• Journal Article Type: Article
• Acceptance Date: Jun 21, 2021
• Publication Date: Jul 14, 2021
• Deposit Date: Jul 15, 2021
• Publicly Available Date: Jul 15, 2021
• Journal: Scientific Reports
• Print ISSN: 2045-2322
• Publisher: Nature Publishing Group
• Volume: 11
• Issue: 1
• Pages: 14456
• DOI: https://doi.org/10.1038/s41598-021-93531-y
• Publisher URL: https://doi.org/10.1038/s41598-021-93531-y
• Related Public URLs: https://www.nature.com/srep
• Additional Information: Additional Information : ** From Springer Nature via Jisc Publications Router ** Licence for this article: http://creativecommons.org/licenses/by/4.0/ **Journal IDs: eissn 2045-2322 **Article IDs: publisher-id: s41598-021-93531-y; manuscript: 93531 **History: collection 12-2021; online 14-07-2021; published 14-07-2021; registration 28-06-2021; accepted 21-06-2021; submitted 24-02-2021; Funders : Qatar Biomedical Research Institute (QBRI) start-up fund; Grant Number: QB13