Open Access

Downregulation of miRNA‑328 promotes the angiogenesis of HUVECs by regulating the PIM1 and AKT/mTOR signaling pathway under high glucose and low serum condition

  • Authors:
    • Yan Zou
    • Fei Wu
    • Qi Liu
    • Xian Deng
    • Rui Hai
    • Xuemei He
    • Xiangyu Zhou
  • View Affiliations

  • Published online on: May 12, 2020     https://doi.org/10.3892/mmr.2020.11141
  • Pages: 895-905
  • Copyright: © Zou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Vascular complications are the primary reason for disability and mortality associated with diabetes mellitus (DM), and numerous microRNAs (miRNAs/miRs) are involved in the process, such as miR‑122, miR‑24 and miR‑423. It has been reported that miR‑328 regulates DM and cardiovascular disease; however, the role and mechanism of action underlying miR‑328 in HUVECs is not completely understood. The present study aimed to investigate the role and mechanism of action underlying the effects of miR‑328 on the functions of HUVECs. To simulate hyperglycemia combined with ischemia‑induced tissue starvation, HUVECs were cultured in endothelial cell medium with 25 mmol/l D‑glucose and 2% FBS for 24 h [high glucose (HG) + 2% FBS group]. HUVEC miR‑328 expression levels were detected by reverse transcription‑quantitative PCR. Cell migration, cytotoxicity and tube‑like structure formation were analyzed using wound healing, Cell Counting Kit‑8 and tube formation assays, respectively. Following transfection with miR‑328 inhibitor, miR‑328 expression was downregulated in HUVECs. Protein expression levels were determined by western blotting. Compared with the control group, the migration and tube‑like structure formation of HUVECs were decreased, and cell cytotoxicity was increased in the HG + 2% FBS group. The protein expression levels of vascular endothelial growth factor were also decreased, and the expression levels of miRNA‑328 in the HG + 2% FBS group were increased compared with the control group. However, miRNA‑328 downregulation reversed the aforementioned effects. Further experiments indicated that the AKT signaling pathway was inhibited in the HG + 2% FBS group; however, miR‑328 downregulation activated the AKT/mTOR signaling pathway, which was blocked by the AKT signaling pathway inhibitor, perifosine. Gene prediction and western blotting demonstrated that miR‑328 displayed a regulatory role via Pim‑1 proto‑oncogene, serine/threonine kinase (PIM1). In conclusion, miR‑328 expression was upregulated and angiogenesis was inhibited when HUVECs were subjected to high glucose and low serum conditions. miR‑328 downregulation enhanced angiogenesis by increasing PIM1 expression and activating the AKT/mTOR signaling pathway in HUVECs under high glucose and low serum conditions.

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August-2020
Volume 22 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

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APA
Zou, Y., Wu, F., Liu, Q., Deng, X., Hai, R., He, X., & Zhou, X. (2020). Downregulation of miRNA‑328 promotes the angiogenesis of HUVECs by regulating the PIM1 and AKT/mTOR signaling pathway under high glucose and low serum condition. Molecular Medicine Reports, 22, 895-905. https://doi.org/10.3892/mmr.2020.11141
MLA
Zou, Y., Wu, F., Liu, Q., Deng, X., Hai, R., He, X., Zhou, X."Downregulation of miRNA‑328 promotes the angiogenesis of HUVECs by regulating the PIM1 and AKT/mTOR signaling pathway under high glucose and low serum condition". Molecular Medicine Reports 22.2 (2020): 895-905.
Chicago
Zou, Y., Wu, F., Liu, Q., Deng, X., Hai, R., He, X., Zhou, X."Downregulation of miRNA‑328 promotes the angiogenesis of HUVECs by regulating the PIM1 and AKT/mTOR signaling pathway under high glucose and low serum condition". Molecular Medicine Reports 22, no. 2 (2020): 895-905. https://doi.org/10.3892/mmr.2020.11141