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-, MCPyVand
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 vmiRNAs
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.
