• Circular RNA - A possible connection between human cytomegalovirus and Gastric cancer
  • saman saeidi,1 alireza mohebbi,2,* reyhane shaddel,3
    1. golestan university of medical sciences(goums)
    2. golestan university of medical sciences(goums)
    3. golestan university of medical sciences(goums)


  • Introduction: Circular RNAs (circRNAs) are a type of single-stranded RNA formed as a covalently closed-loop by connection between the 3ˊ and 5ˊ ends unlike linear RNA form. It’s a spectacular topic that still need more experiments so we can finally discriminate how important they are in humans. Unlike linear RNA, this type of noncoding RNA (ncRNA) is very stable in our bodies. CircRNA was first found in RNA viruses as early as the 1970s.by the functions that circRNAs have like micro RNA sponge, interaction with RNA binding protein(RBP) and regulatory effect on transcription and translation; It has been seen that circular RNAs can play role in many process such as signaling pathways, translation, cell cycle progression. Evidence suggest that circRNAs can be used as biomarker for caners. for example Hsa-circRNA-103809 Promotes Hepatocellular Carcinoma Development via MicroRNA-1270/PLAG1 Like Zinc Finger 2 Axis. given this information, we can focus on effect of circular RNAs on cancers. Cancer can occur due to direct or indirect effect of a microbe. several researches proved there is a bridge between cancers and viruses. These genomic ancient enemies of humans can play role in many aspects of living creatures. One of the substances that they can affect is circular RNA. since there is also connection between cancer and viruses, so why not trying to search about a possible path that viruses can use to cause cancers which is circular RNA pathway.in that case we used human cytomegalovirus relation with gastric cancer.
  • Methods: Systematic Review of published paper in data bases like PUBMED , Google scholar , NCBI and journals like journal of cancer.
  • Results: Human cytomegalovirus and circular RNAs: Clearly relation between viruses and circRNAs is strong even if they don’t owned them. circSP100 shown to be increased during infection by HCMV and helped the infection itself. so viruses do use circRNAs for their own purposes directly. HCMV is the only beta herpes virus known to encode microRNAs that are involved in the regulation of diverse cell processes such as cell proliferation, apoptosis, differentiation, and carcinogenesis. It seems that we have new evidence of HCMV pathogenesis mediated by circRNAs pathways. they found that the host genes corresponding to the differentially expressed circRNAs were mainly involved in the regulation of host cell secretion pathways, cell cycle, and cell apoptosis, so since these RNAs are down/up regulated in HCMV infection, they suggest that maybe circRNAs interact with HCMV DNA replication and latent infection. hsa_circ_0001445 and hsa_circ_0001206 are only two important circRNAs that can be used for diagnosis of HCMV infection among many others. these two are related to prostate cancer and also hsa_0001445 can be used for diagnosis of hepatocellular carcinoma (HCC). Gastric cancer and circular RNAs: Through each major function of circRNA, cancer can be the result. Previous studies have evaluated circRNAs as potential biomarkers for gastric cancer(GC). decrease in the circPVRL3 expression level is associated with the presence of GC. Circular RNA hsa_circ_0010882 promotes the progression of gastric cancer via regulation of the PI3K/Akt/mTOR signaling pathway. Human cytomegalovirus and Gastric cancer: Evidence suggest that HCMV is link to multiple human malignancies like gastric cancer. Human cytomegalovirus protein UL136 regulate IL6/STAT3 pathway, through down-regulation of miR-34c in GC cells. UL135 and 136 are risk factors associated with the development of gastric cancer. According to studies, an HCMV infection appeared to be significantly associated with an increased risk of GIC. The infection site resulting from this virus is within gastrointestinal tract. this connection was first mentioned in 1978.
  • Conclusion: so far we realized that gastric cancer can be related to HCMV and also circular RNAs. Also HCMV shown to have strong effect on many circular RNAs. Given all these information, we can understand the possibility of connection between GC and HCMV mediated by circular RNAs and this could be one of the pathways that this virus use. Many experiment needs to be performed in order to find this connection since there is so many circRNAs in our body. we think by following this path, we can achieve spectacular information about a new pathway that viruses can use against us and make this an opportunity for strike back to viruses.
  • Keywords: circRNA – Human cytomegalovirus(HCMV) – gastric cancer