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MiR-616-3p modulates cell proliferation and migration through targeting tissue factor pathway inhibitor 2 in preeclampsia.
Cell Prolif 2018; 51(5):e12490CP

Abstract

OBJECTIVES

Despite improvements in diagnosis and treatment, preeclampsia (PE) continues to pose a significant risk of maternal and foetal morbidity and mortality if not addressed promptly. An increasing number of studies have suggested that tissue factor pathway inhibitor 2 (TFPI2) acts as a suppressor gene, possibly inhibiting multiple serine proteases affecting cell proliferation and migration. It plays an essential role in the occurrence and development of PE, but the pathogenesis remains unclear.

MATERIALS AND METHODS

In our research, we performed western blotting, immunohistochemistry and qPCR assays to investigate TFPI2 and miR-616-3p expression in preeclamptic placental tissues. Cell assays were performed in HTR-8/SVneo and JEG3 cell lines. Cell proliferation and migration events were investigated by MTT, EdU and transwell assays. In conjunction with bioinformatics analysis, luciferase reporter assays were performed to elucidate the mechanism by which miR-616-3p binds to TFPI2 mRNA.

RESULTS

We established that TFPI2 protein levels were significantly upregulated in PE placental tissues. In addition, we found that miR-616-3p binds specifically to the 3'-UTR region of TFPI2 mRNA. Furthermore, miR-616-3p knockdown or TFPI2 overexpression substantially impaired cell growth and migration, whereas miR-616-3p upregulation or TFPI2 knockdown stimulated cell proliferation and migration. This miR-616-3p/TFPI2 axis was also found to affect the epithelial-mesenchymal transition process in PE.

CONCLUSIONS

Our results demonstrated that TFPI2 plays a vital role in the progression of PE and might provide a prospective therapeutic strategy to mitigate the severity of the disorder.

Authors+Show Affiliations

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China. Department of Obstetrics, Gynecology & Reproductive Sciences, Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT, USA.Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.Department of Oncology, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.Department of Oncology, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.Department of Anatomy, Histology and Embryology, The Research Center for Bone and Stem Cells, Nanjing Medical University, Nanjing, Jiangsu Province, China.Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Shenzhen Hospital, FuTian District, Shenzhen, Guangdong, China.Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30028057

Citation

Xu, Yetao, et al. "MiR-616-3p Modulates Cell Proliferation and Migration Through Targeting Tissue Factor Pathway Inhibitor 2 in Preeclampsia." Cell Proliferation, vol. 51, no. 5, 2018, pp. e12490.
Xu Y, Wu D, Jiang Z, et al. MiR-616-3p modulates cell proliferation and migration through targeting tissue factor pathway inhibitor 2 in preeclampsia. Cell Prolif. 2018;51(5):e12490.
Xu, Y., Wu, D., Jiang, Z., Zhang, Y., Wang, S., Ma, Z., ... Sun, L. (2018). MiR-616-3p modulates cell proliferation and migration through targeting tissue factor pathway inhibitor 2 in preeclampsia. Cell Proliferation, 51(5), pp. e12490. doi:10.1111/cpr.12490.
Xu Y, et al. MiR-616-3p Modulates Cell Proliferation and Migration Through Targeting Tissue Factor Pathway Inhibitor 2 in Preeclampsia. Cell Prolif. 2018;51(5):e12490. PubMed PMID: 30028057.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MiR-616-3p modulates cell proliferation and migration through targeting tissue factor pathway inhibitor 2 in preeclampsia. AU - Xu,Yetao, AU - Wu,Dan, AU - Jiang,Ziyan, AU - Zhang,Yuanyuan, AU - Wang,Sailan, AU - Ma,Zhonghua, AU - Hui,Bingqing, AU - Wang,Jing, AU - Qian,Weiping, AU - Ge,Zhiping, AU - Sun,Lizhou, Y1 - 2018/07/20/ PY - 2018/03/08/received PY - 2018/06/03/accepted PY - 2018/7/22/pubmed PY - 2018/10/3/medline PY - 2018/7/21/entrez SP - e12490 EP - e12490 JF - Cell proliferation JO - Cell Prolif. VL - 51 IS - 5 N2 - OBJECTIVES: Despite improvements in diagnosis and treatment, preeclampsia (PE) continues to pose a significant risk of maternal and foetal morbidity and mortality if not addressed promptly. An increasing number of studies have suggested that tissue factor pathway inhibitor 2 (TFPI2) acts as a suppressor gene, possibly inhibiting multiple serine proteases affecting cell proliferation and migration. It plays an essential role in the occurrence and development of PE, but the pathogenesis remains unclear. MATERIALS AND METHODS: In our research, we performed western blotting, immunohistochemistry and qPCR assays to investigate TFPI2 and miR-616-3p expression in preeclamptic placental tissues. Cell assays were performed in HTR-8/SVneo and JEG3 cell lines. Cell proliferation and migration events were investigated by MTT, EdU and transwell assays. In conjunction with bioinformatics analysis, luciferase reporter assays were performed to elucidate the mechanism by which miR-616-3p binds to TFPI2 mRNA. RESULTS: We established that TFPI2 protein levels were significantly upregulated in PE placental tissues. In addition, we found that miR-616-3p binds specifically to the 3'-UTR region of TFPI2 mRNA. Furthermore, miR-616-3p knockdown or TFPI2 overexpression substantially impaired cell growth and migration, whereas miR-616-3p upregulation or TFPI2 knockdown stimulated cell proliferation and migration. This miR-616-3p/TFPI2 axis was also found to affect the epithelial-mesenchymal transition process in PE. CONCLUSIONS: Our results demonstrated that TFPI2 plays a vital role in the progression of PE and might provide a prospective therapeutic strategy to mitigate the severity of the disorder. SN - 1365-2184 UR - https://www.unboundmedicine.com/medline/citation/30028057/MiR_616_3p_modulates_cell_proliferation_and_migration_through_targeting_tissue_factor_pathway_inhibitor_2_in_preeclampsia_ L2 - https://doi.org/10.1111/cpr.12490 DB - PRIME DP - Unbound Medicine ER -