Long Non-Coding RNA FGD5-AS1 Induced by Chlamydia trachomatis Infection Inhibits Apoptosis via Wnt/β-Catenin Signaling Pathway

Yating Wen; Fangzhen Luo; Lanhua Zhao; Shengmei Su; Wenbo Lei; Yi Liu; Keliang Shi; Zhongyu Li

doi:10.3389/fcimb.2021.701352

Long Non-Coding RNA FGD5-AS1 Induced by Chlamydia trachomatis Infection Inhibits Apoptosis via Wnt/β-Catenin Signaling Pathway

Front Cell Infect Microbiol. 2021 Sep 9:11:701352. doi: 10.3389/fcimb.2021.701352. eCollection 2021.

Authors

Yating Wen¹, Fangzhen Luo¹, Lanhua Zhao¹, Shengmei Su¹, Wenbo Lei¹, Yi Liu¹, Keliang Shi¹, Zhongyu Li¹

Affiliation

¹ Institute of Pathogenic Biology, Hengyang Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China.

Abstract

Background: Chlamydia trachomatis (Ct) is one of the most common bacterial sexually transmitted infection (STI) pathogens in the world, but the exact pathogenic mechanism still needs to be further elucidated. Long non-coding RNAs (lncRNAs) have become vital regulators in many biological processes. Their role in the interaction between Ct and host cells has not been reported.

Methods: Microarrays were used to study the expression profiles of lncRNAs and mRNAs in HeLa cells at 12, 24, and 40 h post-infection (hpi). Differentially expressed lncRNAs and mRNAs were verified by RT-qPCR. Coding-non-coding (CNC) network analysis showed co-expression molecules of selected lncRNA. Western blot, flow cytometry, and indirect immunofluorescence were used to detect the effect of lncRNA FGD5-AS1 on apoptosis during Ct infection.

Results: Compared with the uninfected group, the number of differential lncRNAs were 2,130, 1,081, and 1,101 at 12, 24, and 40 hpi, and the number of differential mRNAs was 1,998, 1,129, and 1,330, respectively. Ct induced differential expression of large amounts of lncRNAs and mRNAs in HeLa cells, indicating that lncRNAs may play roles in the pathogenesis of Ct. RT-qPCR verified six differential lncRNAs and six differential mRNAs, confirming the reliability of the microarray. Among these molecules, lncRNA FGD5-AS1 was found to be upregulated at 12 and 24 hpi. Coding-non-coding (CNC) network analysis showed that co-expressed differential molecules of FGD5-AS1 at 12 and 24 hpi were enriched in the DNA replication and Wnt signaling pathway. The downregulation of FGD5-AS1 decreased the expression of β-catenin and inhibited the translocation of β-catenin and the DNA replication, while it promoted apoptosis of the host cells.

Conclusions: DNA replication and apoptosis of host cells were affected by upregulating FGD5-AS1 via Wnt/β-catenin pathway during Ct infection. This study provides evidence that lncRNAs are involved in the coaction between Ct and hosts, and provides new insights into the study of lncRNAs that regulate chlamydial infection.

Keywords: Chlamydia trachomatis; FGD5-AS1; Wnt/β-catenin signaling pathway; apoptosis; long non-coding RNA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis*
Cell Proliferation
Chlamydia Infections / genetics*
Chlamydia trachomatis / genetics
Guanine Nucleotide Exchange Factors
HeLa Cells
Humans
RNA, Long Noncoding* / genetics
Reproducibility of Results
Wnt Signaling Pathway*

Substances

FGD5 protein, human
Guanine Nucleotide Exchange Factors
RNA, Long Noncoding