Hull Rodney, Marima Rahaba, Alaouna Mohammed, Demetriou Demetra, Reis Rui Manuel, Molefi Thulo, Dlamini Zodwa
SAMRC Precision Oncology Research Unit (PORU), DSI/NRF SARChI Chair in Precision Oncology and Cancer Prevention (POCP), Pan African Cancer Research Institute (PACRI), University of Pretoria, Hatfield 0028, South Africa.
Department of Internal Medicine, Faculty of Health Sciences, School of Clinical Medicine, University of the Witwatersrand, Parktown 2193, South Africa.
Microorganisms. 2022 Jul 18;10(7):1448. doi: 10.3390/microorganisms10071448.
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.
大约15%的人类癌症具有病毒病因。尽管已取得进展，但了解病毒致癌作用及相关分子机制仍很复杂。细胞微小RNA（miRNA）的发现带来了重大突破。有趣的是，人们还发现病毒也能编码自身的miRNA。这些病毒来源的小非编码miRNA也被称为病毒miRNA（v-miRNA）。尽管v-miRNA的功能在很大程度上仍有待阐明，但其在肿瘤发生中的作用不可忽视。v-miRNA还被证明利用细胞机制来促进病毒复制和存活。虽然丙型肝炎病毒（HCV）及其病毒miRNA的发现仍在进行中，但人乳头瘤病毒（HPV）、EB病毒（EBV）、乙型肝炎病毒（HBV）、 Merkel细胞多瘤病毒（MCPyV）和卡波西肉瘤相关疱疹病毒（KSHV）编码的miRNA的存在已得到证实。v-miRNA已被证明可靶向宿主因子以促进肿瘤发生、逃避和抑制免疫系统，以及失调细胞周期和凋亡机制。尽管v-miRNA诱导肿瘤发生的确切机制仍不清楚，但v-miRNA在肿瘤发生、病毒潜伏和细胞转化中起着积极作用。此外，v-miRNA可作为病毒和宿主基因的转录后基因调节因子。因此，有人提出v-miRNA可能作为具有病毒病因癌症的诊断生物标志物和治疗靶点。尽管其临床应用存在重大挑战，但新出现的报告表明它们在精准医学中发挥着重要作用。本综述将重点关注HPV、HCV、EBV、HBV、MCPyV和KSHV产生的v-miRNA在肿瘤发生中的作用、作为免疫逃避效应因子的作用、作为诊断生物标志物的作用以及作为新型抗癌治疗靶点的作用。最后，将讨论v-miRNA在精准肿瘤学中的诊疗相关挑战和机遇。
