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MALAT1 sponges miR-26a and miR-26b to regulate endothelial cell angiogenesis via PFKFB3-driven glycolysis in early-onset preeclampsia.

ABSTRACT: 6-phosphofructo-2-kinase (PFKFB3) is a crucial regulator of glycolysis that has been implicated in angiogenesis and the development of diverse diseases. However, the functional role and regulatory mechanism of PFKFB3 in early-onset preeclampsia (EOPE) remain to be elucidated. According to previous studies, noncoding RNAs play crucial roles in EOPE pathogenesis. The goal of this study was to investigate the functional roles and co-regulatory mechanisms of the metastasis-associated lung adenocarcinoma transcript-1 (MALAT1)/microRNA (miR)-26/PFKFB3 axis in EOPE. In our study, decreased MALAT1 and PFKFB3 expression in EOPE tissues correlates with endothelial cell (EC) dysfunction. The results of in vitro assays revealed that PFKFB3 regulates the proliferation, migration, and tube formation of ECs by modulating glycolysis. Furthermore, MALAT1 regulates PFKFB3 expression by sponging miR-26a/26b. Finally, MALAT1 knockout reduces EC angiogenesis by inhibiting PFKFB3-mediated glycolysis flux, which is ameliorated by PFKFB3 overexpression. In conclusion, decreased MALAT1 expression in EOPE tissues reduces the glycolysis of ECs in a PFKFB3-dependent manner by sponging miR-26a/26b and inhibits EC proliferation, migration, and tube formation, which may contribute to abnormal angiogenesis in EOPE. Thus, strategies targeting PFKFB3-driven glycolysis may be a promising approach for the treatment of EOPE.

SUBMITTER: Li Q

PROVIDER: S-EPMC7868745 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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MALAT1 sponges miR-26a and miR-26b to regulate endothelial cell angiogenesis via PFKFB3-driven glycolysis in early-onset preeclampsia.

Li Qi Q Liu Xiaoxia X Liu Weifang W Zhang Yang Y Wu Mengying M Chen Zhirui Z Zhao Yin Y Zou Li L

Molecular therapy. Nucleic acids 20210116

6-phosphofructo-2-kinase (PFKFB3) is a crucial regulator of glycolysis that has been implicated in angiogenesis and the development of diverse diseases. However, the functional role and regulatory mechanism of PFKFB3 in early-onset preeclampsia (EOPE) remain to be elucidated. According to previous studies, noncoding RNAs play crucial roles in EOPE pathogenesis. The goal of this study was to investigate the functional roles and co-regulatory mechanisms of the metastasis-associated lung adenocarci ...[more]

PMID: 33614238

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Project description:Vitamin D insufficiency or deficiency during pregnancy has been associated with an increased risk of preeclampsia. Increased placental cyclooxygenase-2 (COX-2) activity was proposed to contribute to the inflammatory response in preeclampsia. This study was to investigate if vitamin D can benefit preeclampsia by inhibiting placental COX-2 expression. Placenta tissues were obtained from 40 pregnant women (23 normotensive and 17 preeclampsia). miR-26b-5p expression was assessed by quantitative PCR. Vitamin D receptor (VDR) expression and COX-2 expression were determined by immunostaining and Western blot. HTR-8/SVneo trophoblastic cells were cultured in vitro to test anti-inflammatory effects of vitamin D in placental trophoblasts treated with oxidative stress inducer CoCl2. 1,25(OH)2D3 was used as bioactive vitamin D. Our results showed that reduced VDR and miR-26b-5p expression, but increased COX-2 expression, was observed in the placentas from women with preeclampsia compared to those from normotensive pregnant women. Transient overexpression of miR-26b-5p attenuated the upregulation of COX-2 expression and prostaglandin E2 (PGE2) production induced by CoCl2 in placental trophoblasts. 1,25(OH)2D3 treatment inhibited CoCl2-induced upregulation of COX-2 in placental trophoblasts. Moreover, miR-26b-5p expression were significantly upregulated in cells treated with 1,25(OH)2D3, but not in cells transfected with VDR siRNA. Conclusively, downregulation of VDR and miR-26b-5p expression was associated with upregulation of COX-2 expression in the placentas from women with preeclampsia. 1,25(OH)2D3 could promote miR-26b-5p expression which in turn inhibited COX-2 expression and PGE2 formation in placental trophoblasts. The finding of anti-inflammatory property by vitamin D through promotion of VDR/miR-26b-5p expression provides significant evidence that downregulation of vitamin D/VDR signaling could contribute to increased inflammatory response in preeclampsia.

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Dataset Information

MALAT1 sponges miR-26a and miR-26b to regulate endothelial cell angiogenesis via PFKFB3-driven glycolysis in early-onset preeclampsia.

Publications

MALAT1 sponges miR-26a and miR-26b to regulate endothelial cell angiogenesis via PFKFB3-driven glycolysis in early-onset preeclampsia.

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