• Interplay between Viruses & Human microRNAs: Implications for Cancer Pathogenesis
  • Pourya Rastin,1 Tayyebeh Halakoo,2 Sama Seyedi,3 Rozita Ghojoghi,4,*
    1. Shahrood Islamic Azad University
    2. Gonbad Kavoos Islamic Azad University
    3. Gonbad Kavoos Islamic Azad University
    4. Shiraz University of Medical Sciences


  • Introduction: Recent studies have demonstrated that certain viruses are capable of disrupting gene expression regulation and thereby participate in tumorigenesis processes. In recent years, increasing attention has been directed toward the role of microRNAs (miRNAs) as post-transcriptional regulators of gene expression. These short non-coding RNAs can modulate cellular functions such as proliferation, survival, and oncogenesis by inhibiting translation or inducing degradation of target mRNAs. Oncogenic viruses, including Epstein-Barr Virus (EBV), Human Papillomavirus (HPV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), and Kaposi's Sarcoma-associated Herpesvirus (KSHV), possess the ability to perturb cellular regulatory balance through the production of viral miRNAs (v-miRNAs), which enable infected cells to evade immune detection without producing antigens. Conversely, host cellular miRNAs also play critical roles in regulating gene expression and responding to stressors related to cancer development. Based on their functional roles, miRNAs are classified into tumor suppressors and oncogenes, and alterations in their expression levels are among the hallmark features of many cancers. This review examines the dual functions of viral and cellular miRNAs in tumorigenesis, with particular emphasis on oncogenic viruses such as KSHV, HBV, EBV, MCPyV, HCV, and HPV.
  • Methods: A comprehensive literature review was conducted by systematically searching databases such as PubMed and Scopus for studies published up to October 2025.
  • Results: Viruses produce their own miRNAs (v-miRNAs) using mechanisms similar to their host cells, requiring active Dicer and Drosha enzymes. HPV 16 (miR-H1, H2, H3, H5, H6), HPV 35, 38, 68 (miR-H1), have influence on immune evasion and cell cycle proliferation. HBV microRNAs which have influence on ontogenesis by cell proliferations are HBV-miR-2 and 3. MCPyV mircoRNAs which can cause cancer by immune evasion and viral proliferations are MCV-miR-M1-3P and 5P. V-miRNAs in some viruses like EBV and KSHV has more complicated effect on human cells such as immune evasion, angiogenesis, anti-apoptosis, tumorigenesis, viral latency, proliferative, pro-metastatic, differentiation, regulation of lytic induction, cell migration and evasion. Oncogenic EBV microRNAs are ebv-BART (3-3p, 4-5p, 5-5p, 6-3p, 6-5p, 2-5p, 17-5p, 22, 1-5p, 1-3p, 8, 9, 11, 10-3p, 13-3p, 15, 16, 20-5p), ebv-BHRF (1-1, 1-2 and 1-3). Also oncogenic KSHV microRNAs are kshv-miR-k (3, 4, 12-1-5p, 12-1, 12-3, 12-4, 12-5, 12-6, 12-4-5p, 12-9, 12-7, 12-11, 12-10a, 12-10b, 4-5p, 1-5p, 5, 7-5p, 9-5p). Hepatitis B Virus encodes miRNAs that modulate viral replication and host cell pathways, acting as both tumor suppressors (HBV-miR-2 targeting TRIM35) and oncogenes (targeting RAN), thereby influencing hepatocarcinogenesis. In contrast, Hepatitis C Virus influences host miRNAs, most notably miR-122, to enhance viral replication, though viral-encoded miRNAs have not been definitively identified. Overall, these viruses utilize encoded miRNAs to regulate viral life cycles, manipulate host pathways, and promote oncogenesis, though ongoing research continues to elucidate their precise roles.
  • Conclusion: In summary, viruses such as EBV, HPV, HBV, HCV, and KSHV have developed ways to produce their own microRNAs, which help them evade immune responses and promote cancer development. Additionally, host cell microRNAs also play a crucial role in controlling cell growth and preventing or encouraging tumor formation. Understanding how viral and cellular microRNAs interact offers important insights into cancer mechanisms and could lead to new strategies for diagnosis and treatment.
  • Keywords: MicroRNA, Oncogenic Viruses, Cancer