MiR-15p-5p Mediates the Coordination of ICAM-1 and FAK to Promote Endothelial Cell Proliferation and Migration

Gu, Wei; Zhang, Li; Zhang, Xinhua; Wang, Binyu; Shi, Xiaoyu; Hu, Kang; Ye, Yingying; Liu, Guoquan

doi:10.1007/s10753-022-01630-3

Cited by 3 publications

(2 citation statements)

References 38 publications

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“…Moreover, miR-25 contributed to the treatment of sepsis, as well as miR-22-3p, which might be regarded as an early diagnostic biomarker for septic conditions [ 61 ]. MiR-15b-5p notably supports or opposes endothelial migration and proliferation, in both physiological conditions and altered environments as sepsis, by targeting the protein kinase B3 (AKT3) and ICAM1/ focal adhesion kinase (FAK) pathways, respectively [ 62 , 63 ]. The promoting role of miR-15b-5p in hypoxia/reoxygenation and pyroptosis via NLRP3 inflammasome activation and SIRT3 modulation in cardiomyocytes has been described [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

MiR-15b-5p and PCSK9 inhibition reduces lipopolysaccharide-induced endothelial dysfunction by targeting SIRT4

et al. 2023

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Background Endothelial dysfunction and deregulated microRNAs (miRNAs) participate in the development of sepsis and are associated with septic organ failure and death. Here, we explored the role of miR-15b-5p on inflammatory pathways in lipopolysaccharide (LPS)-treated human endothelial cells, HUVEC and TeloHAEC. Methods The miR-15b-5p levels were evaluated in LPS-stimulated HUVEC and TeloHAEC cells by quantitative real-time PCR (qRT–PCR). Functional experiments using cell counting kit-8 (CCK-8), transfection with antagomir, and enzyme-linked immunosorbent assays (ELISA) were conducted, along with investigation of pyroptosis, apoptosis, autophagy, and mitochondrial reactive oxygen species (ROS) by cytofluorometric analysis and verified by fluorescence microscopy. Sirtuin 4 (SIRT4) levels were detected by ELISA and immunoblotting, while proprotein convertase subtilisin-kexin type 9 (PCSK9) expression was determined by flow cytometry (FACS) and immunofluorescence analyses. Dual-luciferase reporter evaluation was performed to confirm the miR-15b-5p–SIRT4 interaction. Results The results showed a correlation among miR-15b-5p, PCSK9, and SIRT4 levels in septic HUVEC and TeloHAEC. Inhibition of miR-15b-5p upregulated SIRT4 content, alleviated sepsis-related inflammatory pathways, attenuated mitochondrial stress, and prevented apoptosis, pyroptosis, and autophagic mechanisms. Finally, a PCSK9 inhibitor (i-PCSK9) was used to analyze the involvement of PCSK9 in septic endothelial injury. i-PCSK9 treatment increased SIRT4 protein levels, opposed the septic inflammatory cascade leading to pyroptosis and autophagy, and strengthened the protective role of miR-15b-5p inhibition. Increased luciferase signal validated the miR-15b-5p–SIRT4 binding. Conclusions Our in vitro findings suggested the miR-15b-5p–SIRT4 axis as a suitable target for LPS-induced inflammatory pathways occurring in sepsis, and provide additional knowledge on the beneficial effect of i-PCSK9 in preventing vascular damage by targeting SIRT4. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

MiR-15b-5p and PCSK9 inhibition reduces lipopolysaccharide-induced endothelial dysfunction by targeting SIRT4

et al. 2023

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“…For example, microRNA miR-15b-5p inhibits FAK expression by binding to the 3′UTR of FAK mRNA. Moreover, intercellular adhesion molecule-1 suppresses miR-15b-5p activity and stimulates endothelial cell proliferation and migration [ 46 ]. The interaction between long noncoding RNA (lncRNA) MIR4435‑2HG and ganglioside synthesis enzyme ST8SIA1 induces the activation of FAK and downstream AKT/β‑catenin signaling, thus promoting prostate cancer cell viability [ 45 ].…”

Section: Fak Structure and Activationmentioning

confidence: 99%

Focal adhesion kinase: from biological functions to therapeutic strategies

Tan,

Yan,

Song

et al. 2023

Exp Hematol Oncol

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Focal adhesion kinase (FAK), a nonreceptor cytoplasmic tyrosine kinase, is a vital participant in primary cellular functions, such as proliferation, survival, migration, and invasion. In addition, FAK regulates cancer stem cell activities and contributes to the formation of the tumor microenvironment (TME). Importantly, increased FAK expression and activity are strongly associated with unfavorable clinical outcomes and metastatic characteristics in numerous tumors. In vitro and in vivo studies have demonstrated that modulating FAK activity by application of FAK inhibitors alone or in combination treatment regimens could be effective for cancer therapy. Based on these findings, several agents targeting FAK have been exploited in diverse preclinical tumor models. This article briefly describes the structure and function of FAK, as well as research progress on FAK inhibitors in combination therapies. We also discuss the challenges and future directions regarding anti-FAK combination therapies.

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ACE2 improves endothelial cell function and reduces acute lung injury by downregulating FAK expression

He,

Gang,

Zhang

et al. 2024

International Immunopharmacology

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MiR-15p-5p Mediates the Coordination of ICAM-1 and FAK to Promote Endothelial Cell Proliferation and Migration

Cited by 3 publications

References 38 publications

MiR-15b-5p and PCSK9 inhibition reduces lipopolysaccharide-induced endothelial dysfunction by targeting SIRT4

MiR-15b-5p and PCSK9 inhibition reduces lipopolysaccharide-induced endothelial dysfunction by targeting SIRT4

Focal adhesion kinase: from biological functions to therapeutic strategies

ACE2 improves endothelial cell function and reduces acute lung injury by downregulating FAK expression

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