miR-15b-AGO2 play a critical role in HTR8/SVneo invasion and in a model of angiogenesis defects related to inflammation

Ming Yang, Yan Chen, Liangju Chen, Ke Wang, Tianying Pan, Xinghui Liu, Wenming Xu
Placenta 2016, 41: 62-73

INTRODUCTION: microRNAs (miRs) have been shown to play critical roles in the regulation of trophoblast and endothelial cell functions, and one significant finding concerning the miR-15/16 family is that most members of this family are highly expressed in endothelial cells and contribute to functions, such as tube formation. The interaction between trophoblast and endothelial cell play an important role in normal placentation process. Therefore, the aims of this study were to investigate the expression of miR-15b in human placenta and to uncover the potential role of miR-15b as well as its target functional loop in trophoblast and endothelial cells. Whether inflammation could modulate the expression of miR-15b and its down-stream target was further investigated. Additionally, the potential link between miR-15b deregulation and preeclampsia was also explored in the placenta of patients diagnosed with preeclampsia.

METHODS: The expression of miR-15b was studied in the placental tissue of a normal pregnancy using in situ hybridization, and the effects of miR-15b on proliferation, invasion, and angiogenesis were further explored in vitro using HTR-8/SVneo and HUVEC cell line models. A Lipopolysaccharides (LPS) treatment model in HTR-8/SVneo cell was utilized to explore the mechanism of how LPS treatment could lead to the activation of miR-15b expression. Western blot was used to detect the expression of proteins related to miR-15b mediated pathway in preeclamptic placentas.

RESULTS: miR-15b inhibits trophoblast cell invasion and endothelial cell tube formation by suppressing the expression of Argonaute 2 (AGO2), a major miRNA effecter protein. AGO2 is specifically localized to human placenta cytotrophoblast and endothelial cells, and it plays important roles in trophoblast cell invasion and endothelial cell tube formation. LPS treatment may lead to the overexpression of miR-15b and down-regulation of AGO2, which may be involved in shallow trophoblast cell invasion associated with the pathogenesis of preeclampsia. Chromatin immunoprecipitation assay indicates that increased occupancy of AGO2 to miR-15b promoter is responsible for the increased expression of miR-15b under the condition of LPS treatment. Furthermore, preeclamptic placentas have decreased expression of AGO2, but increased expression of miR-15b and TLR-4 compared to normal controls.

DISCUSSION: This is the first report about the function of AGO2 in human trophoblast and endothelial cells in the placenta. The data indicates that the aberrant expression of miR-15b contributes to abnormal placentation by targeting AGO2 mRNA. This study provides insight into the potential role of the miR-15b and AGO2 functional loop in the placentation process.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"