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
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.
