LncRNA ZEB1-AS1/miR-1224-5p / MAP4K4 axis regulates mitochondria-mediated HeLa cell apoptosis in persistent Chlamydia trachomatis infection

Fangzhen Luo; Yating Wen; Lanhua Zhao; Shengmei Su; Wenbo Lei; Lili Chen; Chaoqun Chen; Qiulin Huang; Zhongyu Li

doi:10.1080/21505594.2022.2044666

Virulence (Dec 2022)

LncRNA ZEB1-AS1/miR-1224-5p / MAP4K4 axis regulates mitochondria-mediated HeLa cell apoptosis in persistent Chlamydia trachomatis infection

Fangzhen Luo,
Yating Wen,
Lanhua Zhao,
Shengmei Su,
Wenbo Lei,
Lili Chen,
Chaoqun Chen,
Qiulin Huang,
Zhongyu Li

Affiliations

Fangzhen Luo: Institute of Pathogenic Biology, Hengyang Medical School, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang, P. R. China
Yating Wen: Institute of Pathogenic Biology, Hengyang Medical School, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang, P. R. China
Lanhua Zhao: Institute of Pathogenic Biology, Hengyang Medical School, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang, P. R. China
Shengmei Su: Institute of Pathogenic Biology, Hengyang Medical School, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang, P. R. China
Wenbo Lei: Institute of Pathogenic Biology, Hengyang Medical School, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang, P. R. China
Lili Chen: Institute of Pathogenic Biology, Hengyang Medical School, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang, P. R. China
Chaoqun Chen: Institute of Pathogenic Biology, Hengyang Medical School, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang, P. R. China
Qiulin Huang: The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, P. R. China
Zhongyu Li: Institute of Pathogenic Biology, Hengyang Medical School, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang, P. R. China

DOI: https://doi.org/10.1080/21505594.2022.2044666
Journal volume & issue: Vol. 13, no. 1
pp. 444 – 457

Abstract

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Persistent infection of Chlamydia trachomatis is thought to be responsible for the debilitating sequelae of blinding trachoma and infertility. Inhibition of host cell apoptosis is a persistent C. trachomatis infection mechanism. ZEB1-AS1 is a long non-coding RNA (lncRNA), which was up-regulated in persistent C. trachomatis infection in our previous work. In this study, we investigated the role of ZEB1-AS1 in persistent infection and the potential mechanisms. The results showed that ZEB1-AS1 was involved in the regulation of apoptosis, and targeted silencing of ZEB1-AS1 could increase the apoptosis rate of persistently infected cells. Mechanically, interference ZEB1-AS1 caused an apparent down-regulation of the Bcl-2/Bax ratio and the repression of the mitochondrial membrane potential with the remarkable release of cytochrome c, resulting in the significant elevation level of caspase-3 activation. Meanwhile, the luciferase reporter assay confirmed that ZEB1-AS1 acted as a sponge for miR-1224-5p to target MAP4K4. The regulatory effect of miR-1224-5p/MAP4K4 on persistent infection-induced antiapoptosis was regulated by ZEB1-AS1. In addition, ZEB1-AS1 inhibited the apoptosis of Chlamydia-infected cells by activating the MAPK/ERK pathway. In conclusion, we found a new molecular mechanism that the ZEB1-AS1/miR-1224-5p/MAP4K4 axis contributes to apoptosis resistance in persistent C. trachomatis infection. This work may help understand the pathogenic mechanisms of persistent C. trachomatis infection and reveal a potential therapeutic strategy for its treatment.

Published in Virulence

ISSN: 2150-5594 (Print); 2150-5608 (Online)
Publisher: Taylor & Francis Group
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Infectious and parasitic diseases
Website: https://www.tandfonline.com/journals/kvir

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