DLEU2 modulates proliferation, migration and invasion of platelet-derived growth factor-BB (PDGF-BB)-induced vascular smooth muscle cells (VSMCs) via miR-212-5p/YWHAZ axis

ABSTRACT

DLEU2 has been proved to act as an oncogene in a variety of cancers, but its role in cardiovascular diseases is dearth of research. Thus, this study mainly discussed the effect and possible mechanism of DLEU2 on platelet-derived growth factor-BB (PDGF-BB)-triggered vascular smooth muscle cell (VSMC) injury. To obtain authentic results, the expressions of target genes in atherosclerosis serum were determined by reverse transcription quantitative PCR (RT-qPCR) and the protein levels were evaluated by Western blot. PDGF-BB was used to simply simulate the biological characteristics of VSMCs in vitro. The effect of DLEU2 on the biological behavior of PDGF-BB-induced VSMCs was analyzed by gain- and loss-of-function assays. Bioinformatics analysis, dual luciferase reporter assay, and Pearson correlation method were conducted to determine the relationship between target genes. The role of DLEU2/miR-212-5p/ YWHAZ (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta) axis in PDGF-BB-induced VSMCs was verified by rescue experiments. As a result, DLEU2 and YWHAZ were up-regulated, and miR-212-5p was down-regulated in atherosclerosis serum. Overexpressed DLEU2 facilitated the biological behavior of PDGF-BB-induced VSMCs, whilst siDLEU2 did the opposite. Moreover, overexpressed DLEU2 promoted proliferating cell nuclear antigen (PCNA) expression but repressed α-smooth muscle actin (α-SMA) and Calponin expressions, while it also enhanced YWHAZ expression via suppressing miR-212-5p. MiR-212-5p mimic and siYWHAZ reversed the effects of overexpressed DLEU2 on above biological characteristics and protein expressions in PDGF-BB-induced VSMCs, while the regulatory effect of miR-212-5p mimic was partially offset by overexpressed YWHAZ. Collectively, DLEU2 modulates PDGF-BB-induced VSMC injury via miR-212-5p/YWHAZ axis in atherosclerosis.

KEYWORDS:

• Atherosclerosis
• DLEU2
• vascular smooth muscle cells
• miR-212-5p
• YWHAZ

Authors’ contributions

Substantial contributions to conception and design: Zhiying Zhao

Data acquisition, data analysis and interpretation: Guangming Zhang, Jing Yang, Rui Lu, Haijuan Hu

Drafting the article or critically revising it for important intellectual content: Zhiying Zhao

Final approval of the version to be published: Zhiying Zhao, Guangming Zhang, Jing Yang, Rui Lu, Haijuan Hu

Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of the work are appropriately investigated and resolved: Zhiying Zhao, Guangming Zhang, Jing Yang, Rui Lu, Haijuan Hu

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The analyzed data sets generated during the study are available from the corresponding author on reasonable request.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.