MiR-221-3p is down-regulated in preeclampsia and affects trophoblast growth, invasion and migration partly via targeting thrombospondin 2
Authors: Xiaoming Zhu
Shaohua Zhang
Yuan Ma
Yang Yang
Huirong Li
Jing Li
Journal: Biomedicine & Pharmacotherapy (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Growth; HTR-8/SVeno; Invasion and migration; Preeclampsia; THBS2
Affiliations: Department of Gynecology, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi Province, China., Department of Gynecology and Obstetrics, Baoji Maternity and Child Health Hospital, Baoji, Shaanxi Province, China., Reproductive Medicine Center, Tangdu Hospital, PLA Air Force Medical University (The Fourth Military Medical University), Xi'an, Shaanxi Province, China., Department of Gynecology and Obstetrics, Tangdu Hospital, PLA Air Force Medical University (the Fourth Military Medical University), Xi'an, Shaanxi Province, China., School of Nursing, Xi'an Medical University, Xi'an, Shaanxi Province, China. Electronic address: .

Abstract:  Preeclampsia (PE) is a common obstetrical disorder characterized by hypertension and proteinuria. The aberrant expression of miR-221-3p in placental tissues has been implicated in the pathogenesis of PE. This study examined the role of miR-221-3p in trophoblast growth, invasion and migration, and explored the underlying mechanisms. Our results showed that miR-221-3p was down-regulated in placental tissues from PE patients compared to heathy controls as measured by quantitative real-time PCR assay. CCK-8 assay, Transwell invasion assay and wound healing assay showed that miR-221-3p overexpression promoted trophoblast (HTR-8/SVneo cells) growth, invasion and migration, and knockdown of miR-221-3p exerted the opposite effects. Flow cytometry experiments further demonstrated that miR-221-3p overexpression inhibited apoptosis, increased cell population at S phase, and decreased cell population at G0/G1 phase of HTR-8/SVneo cells; while miR-221-3p knockdown exerted the opposite effects. Bioinformatics prediction and luciferase reporter assay showed that miR-221-3p targeted the 3' untranslated region of thrombospondin 2 (THBS2), and qRT-PCR and western blot assays revealed that miR-221-3p negatively regulated the expression of THBS2 in HTR-8/SVneo cells. Furthermore, overexpression of THBS2 attenuated the in vitro effects of miR-221-3p overexpression on cell growth, invasion and migration of HTR-8/SVneo cells. The clinical sample analysis showed that the mRNA expression levels of THBS2 was significantly increased in placental tissues from PE patients and was negatively correlated with expression levels of miR-221-3p. In summary, our results demonstrated that miR-221-3p was down-regulated in PE, and the in vitro functional assays revealed that miR-221-3p promoted trophoblast growth, invasion and migration partly via targeting THBS2. 

Retracted: No

PubPeer comments:
 Two sets of images in Figure 4 appear to be the same, not just similar. Could the authors please review? *** ![file] , 
 Dear Sir, Thanks for your comment and pointing out the mistake in the figure in our published article. After examining it, we would like to explain that due to limited availability of muscle biopsy, we utilized consecutive (serial) tissue sections for immunohistochemistry with different antibodies that label the sarcolemma. Since such images look very similar, during preparation of the image montage, this mistake has been inadvertently committed due to multiple copy-paste operations. The error is regretted. We have submitted the revised figure 4 with the correct images to the Journal s Editor with a request to consider as a corrigendum. Please note that this corrigendum in no way affects the overall outcome and conclusion of the study. Thanks again for bringing this to our attention. Best regards, M.M. Srinivas Bharath (Corresponding Author) , 
 #2 Thank you for your reply and plan for updating the figure. You may post the correct figure here as well. Do you still have the original data for the Western blot in Figure 2B? The Myosin band in the published figure seems to include a splice. *** ![file] , 
 #3 Thanks. Once the corrigendum is approved by the Journal, I will post the link. Best regards, Bharath ,