Insight into mechanisms of pig lncRNA FUT3-AS1 regulating E. coli F18-bacterial diarrhea

PLoS Pathog. 2022 Jun 13;18(6):e1010584. doi: 10.1371/journal.ppat.1010584. eCollection 2022 Jun.

Abstract

Escherichia coli F18 is a common conditional pathogen that is associated with a variety of infections in humans and animals. LncRNAs have emerged as critical players in pathogen infection, but their role in the resistance of the host to bacterial diarrhea remains unknown. Here, we used piglets as animal model and identified an antisense lncRNA termed FUT3-AS1 as a host regulator related to E. coli F18 infection by RNA sequencing. Downregulation of FUT3-AS1 expression contributed to the enhancement of E. coli F18 resistance in IPEC-J2 cells. FUT3-AS1 knockdown reduced FUT3 expression via decreasing the H4K16ac level of FUT3 promoter. Besides, the FUT3-AS1/miR-212 axis could act as a competing endogenous RNA to regulate FUT3 expression. Functional analysis demonstrated that target FUT3 plays a vital role in the resistance of IPEC-J2 cells to E. coli F18 invasion. A Fut3-knockout mice model was established and Fut3-knockout mice obviously improved the ability of resistance to bacterial diarrhea. Interestingly, FUT3 could enhance E. coli F18 susceptibility by activating glycosphingolipid biosynthesis and toll-like receptor signaling which are related to receptor formation and immune response, respectively. In summary, we have identified a novel biomarker FUT3-AS1 that modulates E. coli F18 susceptibility via histone H4 modifications or miR-212/FUT3 axis, which will provide theoretical guidance to develop novel strategies for combating bacterial diarrhea in piglets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Diarrhea / genetics
  • Escherichia coli / metabolism
  • Escherichia coli Infections* / microbiology
  • Gene Expression Regulation, Neoplastic
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Swine
  • Swine Diseases* / genetics

Substances

  • MicroRNAs
  • RNA, Long Noncoding

Grants and funding

This work was supported by grants from National Natural Science Foundation of China (31702082), Jiangsu Agricultural Science and Technology Innovation Fund (CX(20)1003, CX(20)3011), Key Research and Development Project (Modern Agriculture) of Jiangsu Province (BE2019344, BE2019341), Project funded by China Postdoctoral Science Foundation (2021M702764) and the Priority Academic Program Development of Jiangsu Higher Education Institutions. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.