LncRNA ZEB1-AS1/miR-1224-5p / MAP4K4 Axis Regulates Mitochondria-mediated HeLa Cell Apoptosis in Persistent Infection

Overview

Journal Virulence

Specialty Microbiology

Date 2022 Mar 10

PMID 35266440

Authors

Fangzhen Luo

Yating Wen

Lanhua Zhao

Shengmei Su

Wenbo Lei

Lili Chen

Chaoqun Chen

Qiulin Huang

Zhongyu Li

Affiliations

Soon will be listed here.

Abstract

Persistent infection of is thought to be responsible for the debilitating sequelae of blinding trachoma and infertility. Inhibition of host cell apoptosis is a persistent infection mechanism. ZEB1-AS1 is a long non-coding RNA (lncRNA), which was up-regulated in persistent 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 -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 infection. This work may help understand the pathogenic mechanisms of persistent infection and reveal a potential therapeutic strategy for its treatment.

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