Knockdown of mitotically associated long non-coding RNA dysregulates endothelial function, transcriptome, and proteome

ABSTRACT: Preeclampsia (PE) is a hypertensive pregnancy, which is a leading cause of maternal and fetal morbidity and mortality. PE is characterized by a wide spectrum of endothelial and vascular dysfunction. However, the mechanisms underlying PE-associated endothelial dysfunction remain poorly understood. Long non-coding RNAs (lncRNAs) have been implicated in the pathogenesis of PE. Our recent RNA-seq analysis showed that PE downregulated mitotically associated long non-coding RNA (MANCR, also termed LINC00704) in human umbilical vein endothelial cells (HUVECs). Herin, we tested the hypothesis that knockdown of MANCR dysregulates endothelial function via disrupting transcriptome and proteome using HUVECs as a cell model. RT-qPCR was first conducted to confirm the downregulation of MANCR in PE-HUVECs. MANCR was knocked down in HUVECs from normotensive pregnancy using antisense oligonucleotides (ASOs), following by functional assays. RNA-seq and proteomics were run to determine transcriptomic and proteomic changes. RT-qPCR revealed that PE decreased MANCR by ~9- and 20-fold in male and female HUVECs, respectively. Compared with scrambled ASOs, MANCR ASOs reduced MANCR by 71% and 74% in male and female HUVECs, respectively. Functionally, MANCR ASOs blocked fibroblast growth factor-2 (FGF2)- and vascular endothelial growth factor-A (VEGFA)-stimulated cell proliferation, whereas did not affect cell chemotaxis and tube formation in responses to FGF2 and VEGFA. MANCR ASOs also dysregulated expression of 37 and 39 genes, as well as 97 and 15 proteins, in male and female cells, respectively. Bioinformatics predicted that MANCR-regulated genes and proteins were differently associated with diseases and biological functions, as well as biological processes and molecular functions in male and female HUVECs, many of which are highly relevant to cell mitosis and hypertension. Thus, knockdown of MANCR impairs endothelial function along with cell sex-specific disruption of transcriptome and proteome, contributing to PE-associated endothelial dysfunction.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Endothelial Cell Of Umbilical Vein, Primary Cell

SUBMITTER: Si-yan Zhang  

LAB HEAD: Jing Zheng

PROVIDER: PXD079891 | Pride | 2026-10-08

REPOSITORIES: Pride