MiR-375-mediated suppression of engineered coxsackievirus B3 in pancreatic cells

FEBS Lett. 2020 Feb;594(4):763-775. doi: 10.1002/1873-3468.13647. Epub 2019 Nov 7.


Coxsackievirus B3 (CVB3) has potential as a new oncolytic agent for the treatment of cancer but can induce severe pancreatitis. Here, we inserted target sequences of the microRNA miR-375 (miR-375TS) into the 5' terminus of the polyprotein encoding sequence or into the 3'UTR of the CVB3 strain rCVB3.1 to prevent viral replication in the pancreas. In pancreatic EndoC-βH1 cells expressing miR-375 endogenously, replication of the 5'-miR-375TS virus and that of the 3'-miR-375TS virus was reduced by 4 × 103 -fold and 3.9 × 104 -fold, respectively, compared to the parental rCVB3.1. In colorectal carcinoma cells, replication and cytotoxicity of both viruses were slightly reduced compared to rCVB3.1, but less pronounced for the 3'-miR-375TS virus. Thus, CVB3 with miR-375TS in the 3'UTR of the viral genome may be suitable to avoid pancreatic toxicity.

Keywords: cancer therapy; colorectal cancer; coxsackievirus B3; microRNA; oncolytic virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Base Sequence
  • Cell Line, Tumor
  • Enterovirus B, Human / genetics*
  • Genetic Engineering*
  • HEK293 Cells
  • Humans
  • MicroRNAs / genetics*
  • Pancreas / cytology*
  • Pancreas / virology


  • 3' Untranslated Regions
  • MIRN375 microRNA, human
  • MicroRNAs