title: miR-30c regulates proliferation, apoptosis and differentiation via the Shh signaling pathway in P19 cells.
abstract: MicroRNAs (miRNAs) are small, non-coding single-stranded RNAs that suppress protein expression by binding to the 3' untranslated regions of their target genes. Many studies have shown that miRNAs have important roles in congenital heart diseases (CHDs) by regulating gene expression and signaling pathways. We previously found that miR-30c was highly expressed in the heart tissues of aborted embryos with ventricular septal defects. Therefore, this study aimed to explore the effects of miR-30c in CHDs. miR-30c was overexpressed or knocked down in P19 cells, a myocardial cell model that is widely used to study cardiogenesis. We found that miR-30c overexpression not only increased cell proliferation by promoting cell entry into S phase but also suppressed cell apoptosis. In addition, we found that miR-30c inhibited dimethyl sulfoxide-induced differentiation of P19 cells. miR-30c knockdown, in contrast, inhibited cell proliferation and increased apoptosis and differentiation. The Sonic hedgehog (Shh) signaling pathway is essential for normal embryonic development. Western blotting and luciferase assays revealed that Gli2, a transcriptional factor that has essential roles in the Shh signaling pathway, was a potential target gene of miR-30c. Ptch1, another important player in the Shh signaling pathway and a transcriptional target of Gli2, was downregulated by miR-30c overexpression and upregulated by miR-30c knockdown. Collectively, our study revealed that miR-30c suppressed P19 cell differentiation by inhibiting the Shh signaling pathway and altered the balance between cell proliferation and apoptosis, which may result in embryonic cardiac malfunctions.
authors.affiliation: Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.|State Key Laboratory of Reproductive Medicine, Department of Pediatrics, Nanjing Maternity and Child Health Care Hospital Affiliated with Nanjing Medical University, Nanjing, China.
authors.forename: Xuehua
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Pediatrics, Nanjing Maternity and Child Health Care Hospital Affiliated with Nanjing Medical University, Nanjing, China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Yuzhu
authors.initials: Y
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Pediatrics, Nanjing Maternity and Child Health Care Hospital Affiliated with Nanjing Medical University, Nanjing, China.
authors.forename: Xiaoshan
authors.initials: X
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Pediatrics, Nanjing Maternity and Child Health Care Hospital Affiliated with Nanjing Medical University, Nanjing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Pediatrics, Nanjing Maternity and Child Health Care Hospital Affiliated with Nanjing Medical University, Nanjing, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Pediatrics, Nanjing Maternity and Child Health Care Hospital Affiliated with Nanjing Medical University, Nanjing, China.
authors.forename: Zhangbin
authors.initials: Z
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Pediatrics, Nanjing Maternity and Child Health Care Hospital Affiliated with Nanjing Medical University, Nanjing, China.
authors.forename: Shuping
authors.initials: S
authors.lastname: Han
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D053823:Hedgehog Proteins / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction; D000075746:Zinc Finger Protein Gli2 / Q000235:genetics
chemical_list: C000618551:Gli2 protein, mouse; D053823:Hedgehog Proteins; D035683:MicroRNAs; C534715:Mirn30d microRNA, mouse; D000075746:Zinc Finger Protein Gli2