Yan Lv1, Xun Lu2, Chunyan Li3, Yuru Fan3, Xiaohong Ji3, Wei Long3, Li Meng4, Lan Wu3, Luyao Wang3, Mingming Lv5, Hongjuan Ding6. 1. Department of Breast, Women's Hospital of Nanjing Medical University, The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China; Department of Obstetrics, Women's Hospital of Nanjing Medical University, The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China. 2. Milken School of Public Health, George Washington University, Washington, DC, USA. 3. Department of Obstetrics, Women's Hospital of Nanjing Medical University, The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China. 4. Department of Obstetrics, Women's Hospital of Nanjing Medical University, The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China. Electronic address: menglidoctor@hotmail.com. 5. Department of Breast, Women's Hospital of Nanjing Medical University, The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China. Electronic address: jinanmingming@126.com. 6. Department of Obstetrics, Women's Hospital of Nanjing Medical University, The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China. Electronic address: dinghongjuan_226@163.com.
Abstract
OBJECTIVE: We aimed to explore the expression level and biological function of miR-145-5p in preeclampsia (PE). METHODS: The differentially expressed miRNA/mRNA between normal placentas and PE placentas were screened using the GSE84260 and GSE73374 datasets from the Gene Expression Omnibus Database. The expression of miR-145-5p in PE placentas was detected by qRT-PCR. The CCK-8 assay, wound healing and transwell were carried out to determine the cell growth, migration and invasion when miR-145-5p was overexpressed or inhibited. The real-time quantitative PCR (qRT-PCR), Western Blot and dual-luciferase reporter assays were conducted to preliminarily explore possible mechanisms. RESULTS: A total of 33 miRNAs were found significantly differentially expressed in PE patients, 19 were significantly upregulated and 14 were significantly downregulated. The relative miR-145-5p expression was lower in PE placentas than normal placentas. The viability and invasion were suppressed when miR-145-5p was inhibited in trophoblasts cells, while miR-145-5p overexpression promoted the effectiveness. In addition, mRNA and protein expression of FLT1 in HTR-8/SVneo cell was also downregulated with miR-145-5p overexpression, suggesting that FLT1 is the target gene of miR-145-5p. Consistent with miR-145-5p overexpression, the mRNA and protein expression of FLT1 also were upregulated with miR-145-5p interference. Furthermore, the expression of miR-145-5p was regulated by the Hypoxic conditions. CONCLUSIONS: In conclusion, the results showed miR-145-5p may participate in PE development by affecting the proliferation and invasion of trophoblast cells. This is a new perspective to understand the etiology and pathogenesis of PE, which may provide a new breakthrough for the early prediction and diagnosis of PE.
OBJECTIVE: We aimed to explore the expression level and biological function of miR-145-5p in preeclampsia (PE). METHODS: The differentially expressed miRNA/mRNA between normal placentas and PE placentas were screened using the GSE84260 and GSE73374 datasets from the Gene Expression Omnibus Database. The expression of miR-145-5p in PE placentas was detected by qRT-PCR. The CCK-8 assay, wound healing and transwell were carried out to determine the cell growth, migration and invasion when miR-145-5p was overexpressed or inhibited. The real-time quantitative PCR (qRT-PCR), Western Blot and dual-luciferase reporter assays were conducted to preliminarily explore possible mechanisms. RESULTS: A total of 33 miRNAs were found significantly differentially expressed in PE patients, 19 were significantly upregulated and 14 were significantly downregulated. The relative miR-145-5p expression was lower in PE placentas than normal placentas. The viability and invasion were suppressed when miR-145-5p was inhibited in trophoblasts cells, while miR-145-5p overexpression promoted the effectiveness. In addition, mRNA and protein expression of FLT1 in HTR-8/SVneo cell was also downregulated with miR-145-5p overexpression, suggesting that FLT1 is the target gene of miR-145-5p. Consistent with miR-145-5p overexpression, the mRNA and protein expression of FLT1 also were upregulated with miR-145-5p interference. Furthermore, the expression of miR-145-5p was regulated by the Hypoxic conditions. CONCLUSIONS: In conclusion, the results showed miR-145-5p may participate in PE development by affecting the proliferation and invasion of trophoblast cells. This is a new perspective to understand the etiology and pathogenesis of PE, which may provide a new breakthrough for the early prediction and diagnosis of PE.
Authors: Anna Stejskalová; Victoria Fincke; Melissa Nowak; Yvonne Schmidt; Katrin Borrmann; Marie-Kristin von Wahlde; Sebastian D Schäfer; Ludwig Kiesel; Burkhard Greve; Martin Götte Journal: Sci Rep Date: 2021-02-18 Impact factor: 4.379
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