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LncRNA LINC00281/Annexin A2 Regulates Vascular Smooth Muscle Cell Phenotype Switching via the Nuclear Factor-Kappa B Signaling Pathway

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Abstract

Abnormal phenotype switch in vascular smooth muscle cells (VSMCs) plays an important role in the initiation and progression of vascular proliferative diseases. Annexin A2 (ANXA2), related to the pro-inflammatory response, contributes to the proliferation and migration of VSMCs. This study explored the mechanisms involved in the regulation of VSMC phenotype modulation via ANXA2. The results revealed that ANXA2 promotes the phosphorylation of p65 and co-translocates with p65 into the nucleus, resulting in VSMC proliferation, migration, and dedifferentiation. Based on bioinformatics predictions and RNA immunoprecipitation assays, LINC00281 was confirmed to be an upstream regulator of ANXA2. Taken together, ANXA2, which is negatively regulated by the long noncoding RNA (lncRNA) LINC00281, has significant importance in the regulation of VSMC proliferation, migration, and phenotype switching via the nuclear factor-kappa B (NF-кB) p65 signaling pathway. This indicates that the lncRNA LINC00281/ANXA2/NF-кB p65 signaling pathway might be a new therapeutic target for vascular proliferative diseases.

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Abbreviations

LncRNA:

Long noncoding RNA

ANXA2:

Annexin A2

NF-кB:

Nuclear factor-kappa B

VSMCs:

Vascular smooth muscle cells

CVDs:

Cardiovascular diseases

α-SMA:

α-Smooth muscle actin

OPN:

Osteopontin

PCNA:

Proliferating cell nuclear antigen

PDGF:

Platelet-derived growth factor

DMEM:

Dulbecco’s modified Eagle’s medium

si-NC:

Small interfering negative control RNA

RT-PCR:

Real-time polymerase chain reaction

CCK-8:

Cell counting kit-8

MAPK:

Mitogen-activated protein kinase

IкBα:

Inhibitor of NF-кB-α

PDTC:

Pyrrolidine dithiocarbamate

SVM:

Support vector machine

RF:

Random forest

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Acknowledgements

We thank Dr. S Sun et al., who uploaded the microarray data to the NCBI.

Funding

This work was supported by the National Natural Science Foundation of China (No. 81800363), the Provincial Natural Science Foundation of Fujian (No. 2018J01240), and the Fujian Provincial Medical Innovation Project (No. 2018-CX-4).

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Authors and Affiliations

  1. The Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, China

    Lan Cheng, ReneNfornah Maboh, Gaowei Mao & Hui Chen

  2. Hypertension Laboratory, Fujian Provincial Cardiovascular Disease Institute, Fujian Provincial Hospital, Fuzhou, 350001, China

    Huan Wang, Xiaoying Wu & Hui Chen

Authors
  1. Lan Cheng
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  2. Huan Wang
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  6. Hui Chen
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Contributions

CH designed the whole study; CL, WH, and Nfornah Maboh performed the experiments. MGW and WXY analyzed the data. CL wrote the paper. CH revised and edited the manuscript. All authors read and approved the final version of the manuscript.

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Correspondence to Hui Chen.

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Associate Editor Junjie Xiao oversaw the review of this article

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Cheng, L., Wang, H., Maboh, R. et al. LncRNA LINC00281/Annexin A2 Regulates Vascular Smooth Muscle Cell Phenotype Switching via the Nuclear Factor-Kappa B Signaling Pathway. J. of Cardiovasc. Trans. Res. 15, 971–984 (2022). https://doi.org/10.1007/s12265-022-10242-z

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  • DOI: https://doi.org/10.1007/s12265-022-10242-z

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