MiR-328 targeting PIM-1 inhibits proliferation and migration of pulmonary arterial smooth muscle cells in PDGFBB signaling pathway
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Zhengjiang Qian1,2, Limin Zhang1, Jidong Chen1,2, Yanjiao Li1,2, Kang Kang3, Junle Qu2, Zhiwei Wang3, Yujia Zhai3, Li Li1, Deming Gou1
1Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, Guangdong, 518060, China
2Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, Guangdong, 518060, China
3Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shenzhen University, Shenzhen, Guangdong, 518000, China
Deming Gou, email: [email protected]
Keywords: miR-328, PASMCs, PDGF pathway, PIM-1
Received: April 13, 2016 Accepted: June 13, 2016 Published: July 19, 2016
MicroRNAs (miRNAs) have been recognized to mediate PDGF-induced cell dysregulation, but their exact functions remain to be elucidated. By using a sensitive S-Poly(T) Plus qRT-PCR method, the expression profiling of 1,078 miRNAs were investigated in pulmonary artery smooth muscle cells (PASMCs) with or without PDGFBB stimulation. MiR-328 was found as a prominent down-regulated miRNA, displaying a specific dose- and time-dependent downregulation upon PDGFBB exposure. Functional analyses revealed that miR-328 could inhibit PASMCs proliferation and migration both with and without PDGFBB treatment. The Ser/Thr-protein kinase-1 (PIM-1) was identified as a direct target of miR-328, and functionally confirmed by a rescue experiment. In addition, the decrease of miR-328 by PDGFBB might be due to the increased expression of DNA methylation transferase 1 (DNMT1) and DNA methylation. Finally, serum miR-328 level was downregulated in PAH patients associated with congenital heart disease (CHD- PAH). Overall, this study provides critical insight into fundamental regulatory mechanism of miR-328 in PDGFBB-activited PASMCs via targeting PIM- 1, and implies the potential of serum miR-328 level as a circulating biomarker for CHD- PAH diagnosis.
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