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 (MA-LAT1)/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 PFKFB3mediated 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.

PFKFB3-mediated glycometabolism reprogramming modulates endothelial differentiation and angiogenic capacity of placenta-derived mesenchymal stem cells

“…PFKFB3, also termed placental PFK-2, is well known for the highest kinase activity than bisphosphatase activity (700-fold), thus most favoring the catalytic activity to glycolysis [ 41 , 42 ]. Besides, our research group has reported that PFKFB3 plays a vital role in some pathophysiological changes in the placentas [ 36 , 43 ], including placental vasculature formation [ 44 ]. Given that the features and function of MSCs tend to be affected by the tissues from which MSCs are isolated [ 45 ], glycolytic enzyme PFKFB3 was chosen to be the putative modulator in the subsequent experiments.…”

“…It has been widely acknowledged that PFKFB3 participates in vasculogenesis and angiogenesis via regulating the glycolytic flux in ECs [ 64 ]. We have also reported that PFKFB3 plays a vital role in some pathophysiological changes in the placentas [ 36 , 43 ], including the placental vasculature formation [ 44 ]. Besides, PFKFB3 modulates the glycolysis in pericytes to keep the stability and maturity of vessels [ 78 ].…”

TLR4 Modulates Senescence and Paracrine Action in Placental Mesenchymal Stem Cells via Inhibiting Hedgehog Signaling Pathway in Preeclampsia

“…Human umbilical vein endothelial cells (HUVECs) were isolated from human umbilical cords collected from healthy donors via cesarean section as we reported previously [ 50 ]. The umbilical veins were washed with PBS and then digested with collagenase type I (Sigma, USA) for 15 min at 37°C.…”

Circular RNA circCRKL inhibits the proliferation of acute myeloid leukemia cells via the miR-196a-5p/miR-196b-5p/p27 axis

“…The transfection was performed with lipofectamine 3000 reagent (Invitrogen, CA, USA, Cat no. L3000015) as previously described [ 17 ]. The detailed sequences are provided in Table S2.…”

“…The wild-type (wt) and mutated (mut) sequences of the circCRKL and CDKN1B 3ʹ untranslated regions (UTR) containing miRNA binding regions were amplified and cloned into a pmirGlo vector (Gene Pharma, Shanghai, China). A dual-luciferase assay was conducted as described [ 17 ].…”