Dataset Information

MicroRNA‑524‑5p regulates the proliferation and invasion of HTR‑8/SVneo trophoblasts by targeting NUMB in the Notch signaling pathway.

ABSTRACT: Preeclampsia is a pregnancy disorder that is primarily associated with maternal and neonatal or fetal morbidity and mortality. The discovery of dysregulated microRNAs (miRs) and their roles in preeclampsia has provided new insight into the mechanisms involved in pregnancy‑related disorders. In the present study, quantitative PCR demonstrated that the expression levels of miR‑524‑5p were lower in patients with preeclampsia than those in normal pregnant women. Cell Counting Kit‑8 and Transwell assays indicated that overexpression of miR‑524‑5p promoted the proliferation and invasion of HTR‑8/SVneo cells, whereas inhibition of miR‑524‑5p suppressed HTR‑8/SVneo cell proliferation and invasion. Furthermore, NUMB endocytic adaptor protein (NUMB), a negative regulator of the Notch signaling pathway and a target gene of miR‑524‑5p, limited the effects of miR‑524‑5p on HTR‑8/SVneo cell invasion and migration. The present study demonstrated that miR‑524‑5p regulated the proliferation and invasion of HTR‑8/SVneo cells at least partly by targeting NUMB to regulate the Notch signaling pathway.

SUBMITTER: Zheng L

PROVIDER: S-EPMC8060792 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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MicroRNA‑524‑5p regulates the proliferation and invasion of HTR‑8/SVneo trophoblasts by targeting NUMB in the Notch signaling pathway.

Zheng Linmei L Song Jie J Tang Rong R Chen Xiaoju X Wang Li L Wu Dongcai D Cen Hui H Shi Lei L

Molecular medicine reports 20210413 6

Preeclampsia is a pregnancy disorder that is primarily associated with maternal and neonatal or fetal morbidity and mortality. The discovery of dysregulated microRNAs (miRs) and their roles in preeclampsia has provided new insight into the mechanisms involved in pregnancy‑related disorders. In the present study, quantitative PCR demonstrated that the expression levels of miR‑524‑5p were lower in patients with preeclampsia than those in normal pregnant women. Cell Counting Kit‑8 and Transwell ass ...[more]

PMID: 33846809

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Project description:Trichloroethylene is an industrial solvent and common environmental pollutant. Despite efforts to ban trichloroethylene, its availability and usage persist globally, constituting a hazard to human health. Recent studies reported associations between maternal trichloroethylene exposure and increased risk for low birth weight. Despite these associations, the toxicological mechanism underlying trichloroethylene adverse effects on pregnancy remains largely unknown. The trichloroethylene metabolite S-(1,2-dichlorovinyl)-L-cysteine (DCVC) induces mitochondrial-mediated apoptosis in a trophoblast cell line. To gain further understanding of mitochondrial-mediated DCVC placental toxicity, this study investigated the effects of DCVC exposure on mitochondrial function using non-cytolethal concentrations in placental cells. Human trophoblasts, HTR-8/SVneo, were exposed in vitro to a maximum of 20 μM DCVC for up to 12 h. Cell-based oxygen consumption and extracellular acidification assays were used to evaluate key aspects of mitochondrial function. Following 6 h of exposure to 20 μM DCVC, elevated oxygen consumption, mitochondrial proton leak and sustained energy coupling deficiency were observed. Similarly, 12 h of exposure to 20 μM DCVC decreased mitochondrial-dependent basal, ATP-linked and maximum oxygen consumption rates. Using the fluorochrome TMRE, dissipation of mitochondrial membrane potential was detected after a 12-h exposure to 20 μM DCVC, and (±)-α-tocopherol, a known suppressor of lipid peroxidation, attenuated DCVC-stimulated mitochondrial membrane depolarization but failed to rescue oxygen consumption perturbations. Together, these results suggest that DCVC caused progressive mitochondrial dysfunction, resulting in lipid peroxidation-associated mitochondrial membrane depolarization. Our findings contribute to the biological plausibility of DCVC-induced placental impairment and provide new insights into the role of the mitochondria in DCVC-induced toxicity.

Project description:Retinoblastoma (RB) is one of the most common forms of childhood intraocular cancer. While the occurrence of RB is traditionally associated with dysregulation of the RB1 gene, efforts have been made to assess the role of several other pathways that may result in RB. The Notch signaling pathway has been identified as one of the sentinel pathways in retinal development and has been indicated to serve as a tumor suppressor. However, epigenetic modifications of the Notch signaling pathway, and their consequences on tumor establishment and progression, have received little attention. The present study attempted to elucidate the microRNA (miR)-mediated dysregulation of the Notch signaling pathway and its implications on tumor initiation. Upon recruitment of patients with RB (age, 4-25 months), the levels of miR-34b-5p were determined in tumor and adjacent healthy tissues. Simultaneously, the serum levels of miR-34b-5p were measured in tumor and healthy samples using reverse transcriptase-quantitative PCR (RT-qPCR). Binding of miR-34b-5p to Notch1 and Notch2 were confirmed bioinformatically. In vitro studies were performed in Y79 and Weri-Rb-1 RB cell lines. The cell lines were transfected with miR-34b-5p constructs and miR-34b-5p overexpression was confirmed using RT-qPCR. The impact of miR-34b-5p overexpression on cell growth and cancer stemness markers (Sox-2, Nanog, and CD133) was examined. The expression levels of Notch1 and Notch2 were evaluated in the presence of miR-34b-5p. The rescue of cell growth and cancer stemness phenotypes was evaluated by co-transfection of miR-34b-5p with Notch1 or Notch2. The results of the present study indicated that the expression levels of miR-34b-5p were reduced in patient tissues and serum samples compared with those in healthy tissues and samples. Notch1 and Notch2 expression level was negatively correlated with the expression level of miR-34b-5p. Overexpression of miR-34b-5p resulted in reduced cell proliferation, migration, invasion and cancer stemness compared with the control group. Further in vivo experiments confirmed the inhibitory effects of miR-34b-5p on RB cell proliferation. Upon co-transfection of miR-34b-5p with Notch1 or Notch2, these phenotypes were rescued with reversal of cell growth and tumor sphere formation. Collectively, the results indicated that miR-34b-5p functions as a tumor suppressor in RB via regulating the Notch signaling pathway. Therefore, miR-34b-5p may be explored for its utility as a therapeutic target in RB.

Dataset Information

MicroRNA‑524‑5p regulates the proliferation and invasion of HTR‑8/SVneo trophoblasts by targeting NUMB in the Notch signaling pathway.

Publications

MicroRNA‑524‑5p regulates the proliferation and invasion of HTR‑8/SVneo trophoblasts by targeting NUMB in the Notch signaling pathway.

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