Computational Analysis of Epstein-Barr Virus BamH1 A Rightward Transcript (BART) MicroRNA (miRNA) Regulation on Messenger and Long Non-Coding RNAs in Nasopharyngeal Cancer

Daphne Olivia Jawai, Sadai (2024) Computational Analysis of Epstein-Barr Virus BamH1 A Rightward Transcript (BART) MicroRNA (miRNA) Regulation on Messenger and Long Non-Coding RNAs in Nasopharyngeal Cancer. Masters thesis, Universiti Malaysia Sarawak (UNIMAS).

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Abstract

The interaction and regulation amongst messenger RNA (mRNA), microRNA (miRNA) and long non-coding RNA (lncRNA) have been identified as causative of nasopharyngeal cancer (NPC) when their expression levels are dysregulated by each other and affecting the biological and molecular functions of affected nasopharynx cells. This interaction is known as competing endogenous RNA (ceRNA) regulatory activity. However, the study of regulation mechanisms of BamHI A rightward transcript (BART) miRNAs encoded by Epstein-Barr virus (EBV) on ceRNA in the pathogenesis of NPC is unavailable. According to previous studies, the Epstein-Barr virus was deemed one of NPC causative factors through its regulation of ceRNA activity using BART miRNAs. Therefore, in this study, candidate BART miRNAs, mRNAs, miRNAs and lncRNAs were obtained by integrating multi-level RNAs expressions data through bioinformatics analysis by constructing the cross-regulatory network. The cross-regulatory network was the combination of mRNA-miRNA-lncRNA ceRNA network with EBV miRNAs-mRNAs network. The result revealed six EBV miRNAs (ebv-miR-BART21-3p, ebv-miR-BART19-3p, ebv-miR-BART15, ebv-miR-BART2-5p, ebv-miR-BART20-3p and ebv-miR-BART11-5p) were interacting with four mRNAs (EYA4, EYA1, EBF1 and MACROD2). In addition, these mRNAs were interacting with six miRNAs (hsa-miR-1246, hsa-miR-93-5p, hsa-miR-16-5p, hsa-miR-135b-5p, hsa-miR-211-5p and hsa-miR-1305) where these miRNAs were interacting with three lncRNAs which are CASC2, TPTE2P1 and ARHGEF26-AS1. The data attained showed that these BART miRNAs may deregulate these mRNAs and affect the expressions of both miRNAs and lncRNAs. This gives insight into understanding the regulatory mechanisms of BART miRNAs on ceRNA activity. This study also revealed the potential functions of BART miRNAs and lncRNAs acting similarly as either tumour suppressors or oncogenes. Furthermore, the data obtained suggested that BART miRNAs affect DNA repair regulation and apoptosis in NPC by down-regulating the mRNAs, which pertains to poor overall survival (OS) in NPC patients. Overall, these findings exhibited the potential role of these BART miRNAs, mRNAs and lncRNAs as diagnostic and prognostic biomarkers in EBV-induced NPC carcinogenesis based on their ability to target and regulate the expressions of each other.

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