Downregulation of the long non-coding RNA MALAT1 in tenofovir-treated pregnant women with hepatitis B virus infection promotes immune recovery of natural killer cells via the has-miR-155-5p/HIF-1α axis
Fanfan Guo, Yufei Yuan, Ziyi Chen, Fan Gao, Xia Li, Hongyan Wang, Xiaona Wang, Guiqin Bai
Abstract
BACKGROUND: Currently, tenofovir disoproxil fumarate (TDF) treatment in pregnant women with hepatitis B virus (HBV) infection in the second trimester of pregnancy to reduce the HBV DNA load and block the mother-to-child transmission of HBV has become a consensus. An increasing number of studies have shown that lncRNAs play an important role in immune regulation; however, there are only a few studies on how lncRNAs affect the immune function of TDF-treated pregnant women with HBV infection. METHODS: The peripheral blood of pregnant women with HBV infection was collected before and after TDF treatment for whole-transcriptome sequencing; the differential expression of lncRNA MALAT1 in PBMCs and natural killer (NK) cells was verified by qRT-PCR. ELISA and flow cytometry were used to detect the effect of MALAT1 on NK-92 cells on IFN-γ secretion. Dual-luciferase reporter, qRT-PCR, and western blot analyses were used to verify the relationship between the expression levels of MALAT1, has-miR-155-5p and HIF-1α. RESULTS: After TDF treatment, the MALAT1 expression in the PBMCs of pregnant women with HBV infection, especially in NK cells, was significantly reduced. MALAT1 overexpression decreased IFN-γ secretion in NK-92 cells, while IFN-γ secretion increased after MALAT1 knockdown. Mechanistically, we identified MALAT1 as a competitive endogenous RNA that regulates HIF-1α expression by sponging has-miR-155-5p. Low HIF-1α expression resulted in increased IFNG expression in, and IFN-γ secretion by, NK cells. CONCLUSIONS: Thus, MALAT1 may play an important role in NK cell-mediated immunity in TDF-treated pregnant women with HBV infection by regulating the has-miR-155-5p/HIF-1α axis.