IMR Press / FBL / Volume 27 / Issue 12 / DOI: 10.31083/j.fbl2712330
Open Access Original Research
LncRNA HIF1A-AS1 Regulates the Cellular Function of HUVECs by Globally Regulating mRNA and miRNA Expression
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1 Department of Orthopaedics, The First Affiliated Hospital of Kunming Medical University, 650032 Kunming, Yunnan, China
*Correspondence: chenlqkm@sina.com (Lingqiang Chen)
These authors contributed equally.
Academic Editor: Ioanna-Katerina Aggeli
Front. Biosci. (Landmark Ed) 2022, 27(12), 330; https://doi.org/10.31083/j.fbl2712330
Submitted: 8 September 2022 | Revised: 1 November 2022 | Accepted: 15 November 2022 | Published: 21 December 2022
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Background: Long non-coding RNA (lncRNA) hypoxia inducible factor 1α-antisense RNA 1 (HIF1A-AS1) serves critical roles in cardiovascular diseases (CVDs). Vascular endothelial cells (VECs) are vulnerable to stimuli. Our previous study revealed that knockdown of HIF1A-AS1 reduces palmitic acid-induced apoptosis and promotes the proliferation of human VECs (HUVECs); however, the underlying mechanism remains unclear. Material and Methods: Cell Counting Kit-8, flow cytometry, transwell invasion, and wound healing were applied to detect the function of HUVECs. Moreover, miRNA sequencing (miRNA-seq) and RNA sequencing (RNA-seq) were conducted to uncover its underlying mechanism. Quantitative Polymerase Chain Reaction (qPCR) was implemented to assess the accuracy of miRNA-seq. A co-expression network was generated to determine the relationship between differentially expressed miRNAs (DEmiRNAs) and differentially expressed genes (DEGs). Results: Knockdown of HIF1A-AS1 promoted the proliferation, migration, and invasion but reduced the apoptosis of HUVECs, and the overexpression of this lncRNA had the opposite effect. Numerous DEmiRNAs and DEGs were identified, which might contribute to this phenomenon. Multiple target genes of DEmiRNAs were associated with cell proliferation and apoptosis, and overlapped with DEGs identified from RNA-seq. Finally, the network manifested that lncRNA HIF1A-AS1 moderated the function of HUVECs by not only regulating the expression of some genes directly but also by influencing a few miRNAs to indirectly mediate the expression of mRNAs. Conclusions: The results suggested that HIF1A-AS1 might regulate HUVEC function by not only regulating the expression of some genes directly but also by influencing some miRNAs to indirectly mediate the expression level of mRNA.

Keywords
HIF1A-AS1
HUVECs
miRNA
mRNA
cardiovascular diseases
Funding
81860093/National Natural Science Foundation of China (NSFC)
81660215/National Natural Science Foundation of China (NSFC)
202101AY070001-031/Associated Project of Yunnan Province Science & Technology Department and Kunming Medical University Basic Research for Application
2019FE001(-207)/Associated Project of Yunnan Province Science & Technology Department and Kunming Medical University Basic Research for Application
202101AT070226/Associated Project of Yunnan Province Science & Technology Department and Kunming Medical University Basic Research for Application
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