title: MiR-328 targeting PIM-1 inhibits proliferation and migration of pulmonary arterial smooth muscle cells in PDGFBB signaling pathway.
abstract: 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.
authors.affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, Guangdong, 518060, China.|Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, Guangdong, 518060, China.
authors.forename: Zhengjiang
authors.initials: Z
authors.lastname: Qian
authors.affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, Guangdong, 518060, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, Guangdong, 518060, China.|Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, Guangdong, 518060, China.
authors.forename: Jidong
authors.initials: J
authors.lastname: Chen
authors.affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, Guangdong, 518060, China.|Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, Guangdong, 518060, China.
authors.forename: Yanjiao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shenzhen University, Shenzhen, Guangdong, 518000, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Kang
authors.affiliation: Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, Guangdong, 518060, China.
authors.forename: Junle
authors.initials: J
authors.lastname: Qu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shenzhen University, Shenzhen, Guangdong, 518000, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shenzhen University, Shenzhen, Guangdong, 518000, China.
authors.forename: Yujia
authors.initials: Y
authors.lastname: Zhai
authors.affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, Guangdong, 518060, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, Guangdong, 518060, China.
authors.forename: Deming
authors.initials: D
authors.lastname: Gou
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000293:Adolescent; D000328:Adult; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D000077214:Becaplermin; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D002478:Cells, Cultured; D002675:Child, Preschool; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006330:Heart Defects, Congenital / Q000097:blood / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D051573:Proto-Oncogene Proteins c-pim-1 / Q000235:genetics* / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000166:cytology; D034622:RNA Interference; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; D043925:Angiogenesis Inducing Agents; C548170:MIRN328 microRNA, human; D035683:MicroRNAs; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; C496634:PIM1 protein, human; D051573:Proto-Oncogene Proteins c-pim-1
keywords: PASMCs; PDGF pathway; PIM-1; miR-328