Viral Encoded miRNAs in Tumorigenesis: Theranostic Opportunities in Precision Oncology

Abstract

About 15% of all human cancers have a viral etiology. Although progress has been made, understanding the viral oncogenesis and associated molecular mechanisms remain complex. The discovery of cellular miRNAs has led to major breakthroughs. Interestingly, viruses have also been discovered to encode their own miRNAs. These viral, small, non-coding miRNAs are also known as viral-miRNAs (v-miRNAs). Although the function of v-miRNAs largely remains to be elucidated, their role in tumorigenesis cannot be ignored. V-miRNAs have also been shown to exploit the cellular machinery to benefit viral replication and survival. Although the discovery of Hepatitis C virus (HCV), and its viral miRNAs, is a work in progress, the existence of HPV-, EBV-, HBV-, MCPyV- and KSHV-encoded miRNA has been documented. V-miRNAs have been shown to target host factors to advance tumorigenesis, evade and suppress the immune system, and deregulate both the cell cycle and the apoptotic machinery. Although the exact mechanisms of v-miRNAs-induced tumorigenesis are still unclear, v-miRNAs are active role-players in tumorigenesis, viral latency and cell transformation. Furthermore, v-miRNAs can function as posttranscriptional gene regulators of both viral and host genes. Thus, it has been proposed that v-miRNAs may serve as diagnostic biomarkers and therapeutic targets for cancers with a viral etiology. Although significant challenges exist in their clinical application, emerging reports demonstrate their potent role in precision medicine. This review will focus on the roles of HPV-, HCV-, EBV-, HBV-, MCPyV-, and KSHV-produced v-miRNAs in tumorigenesis, as effectors in immune evasion, as diagnostic biomarkers and as novel anti-cancer therapeutic targets. Finally, it will discuss the challenges and opportunities associated with v-miRNAs theranostics in precision oncology.

Small non-coding RNAs encoded by RNA viruses: old controversies and new lessons from the COVID-19 pandemic

“…Significant strides have already been made in the pursuit of targeting cellular miRNAs as potential anti-cancer therapeutic agents, and even as innovative drugs. Conversely, the targeting of v-miRNA in tumorigenesis represents a novel approach ( Hull et al, 2022 ). Currently, a cellular miR-122 inhibitor is in a phase II clinical trial ( Janssen et al, 2013 ).…”

Hepatitis B Virus and microRNAs: A Bioinformatics Approach

“…In recent years, several viruses have been found to encode viral microRNAs (v-miRNAs), such as EBV, KSHV, HPV, HSV, MCPyV, HIV, and HBV [67][68][69][70]. At present, a large number of v-miRNAs have been predicted computationally (e.g., SARS CoV-2, HAV, and Nipah [71][72][73]), but only a small part of them have been validated experimentally [74,75].…”