KLF5/LINC00346/miR‑148a‑3p axis regulates inflammation and endothelial cell injury in atherosclerosis

Wang,Fangfang; Ge,Jiyong; Huang,Shenglan; Zhou,Changle; Sun,Zikai; Song,Ying; Xu,Yajing; Ji,Yuan

doi:10.3892/ijmm.2021.4985

KLF5/LINC00346/miR‑148a‑3p axis regulates inflammation and endothelial cell injury in atherosclerosis

Authors:
- Fangfang Wang
- Jiyong Ge
- Shenglan Huang
- Changle Zhou
- Zikai Sun
- Ying Song
- Yajing Xu
- Yuan Ji
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Affiliations: Department of Cardiovascular Disease, Changzhou No. 2 People's Hospital, Affiliated Nanjing Medical University, Changzhou, Jiangsu 213000, P.R. China
Published online on: June 17, 2021 https://doi.org/10.3892/ijmm.2021.4985
Article Number: 152

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Abstract

Atherosclerosis (AS) is the main pathological basis of cardiovascular diseases, which are related to high morbidity and mortality rates. The present study aimed to investigate the role of the Krüppel‑like factor 5 (KLF5)/LINC00346/miR‑148a‑3p loop in AS. The expression levels of KLF5 in serum and of KLF5/LINC00346/miR‑148a‑3p in human umbilical vein endothelial cells (HUVECs) were detected by RT‑qPCR analysis. The protein expression levels of KLF5, phosphorylated (p‑)endothelial nitric oxide synthase (eNOS) and eNOS in HUVECs were analyzed by western blot analysis. Changes in the levels of TNF‑α, IL‑1β, IL‑6 and nitric oxide (NO) were determined in the supernatant through the application of available commercial kits. The binding of KLF5 to the promoter region of LINC00346 was verified by chromatin immunoprecipitation (ChIP)‑PCR assay. The combinatory interaction between KLF5 and LINC00346, LINC00346 and miR‑148a‑3p, and miR‑148a‑3p and KLF5 was confirmed by luciferase reporter assay. The results revealed that KLF5 expression was increased in the serum of patients with AS and also in oxidized low‑density lipoprotein (OX‑LDL)‑stimulated HUVECs. The transcription factor KLF5 promoted the transcription of LINC00346. KLF5 interference or LINC00346 interference inhibited the expression of inflammatory factors and functional injury in OX‑LDL‑stimulated HUVECs. LINC00346 functioned as a sponge of miR‑148a‑3p. miR‑148a‑3p overexpression inhibited the expression of inflammatory factors and functional injury in OX‑LDL‑stimulated HUVECs and miR‑148a‑3p targeted KLF5 expression. On the whole, the present study demonstrates that KLF5 interference induces the downregulation of LINC00346 and also inhibits inflammation and functional injury in OX OX‑LDL‑stimulated HUVECs by upregulating miR‑148a‑3p expression.

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