Hypoxia Inhibits Cell Cycle Progression and Cell Proliferation in Brain Microvascular Endothelial Cells via the miR-212-3p/MCM2 Axis

Shi, Qingqing; Li, Shaohua; Liu, Qiang; Zhang, Shuai; Bai, Yuxiang; Ma, Jin

doi:10.3390/ijms24032788

Cited by 5 publications

(2 citation statements)

References 56 publications

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“…26,27 MCM2 was a member of the protein microchromosome maintenance family and was involved in the regulation of DNA replication and cell cycle. 28 Abnormal expression of MCM2 not only regulated the cycle process and proliferation of cerebral microvascular endothelial cells, 29 but also participated in the self-renewal and pluripotent maintenance of human pluripotent stem cells. 30 Besides, as a proliferative marker, MCM2 was significantly overexpressed in almost all cancers, which was associated with tumor staging in multiple cancers, and played a carcinogenic role.…”

Section: Discussionmentioning

confidence: 99%

KNTC1 knockdown inhibits the proliferation and migration of osteosarcoma cells by MCM2

Zhong,

Dong,

Liu

2024

Molecular Carcinogenesis

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Osteosarcoma (OS) is a common primary malignant bone tumor, and it is necessary to further investigate the molecular mechanism of OS progression. The expression of kinetochore associated protein 1 (KNTC1) and minichromosome maintenance 2 (MCM2) was detected by immunohistochemistry, quantitative PCR (qPCR) and Western blot. Gene knockdown or overexpression cell models were constructed and the proliferation, apoptosis, cell cycle and migration were detected in vitro, besides, xenograft models were established to explore the effects of KNTC1 downregulation in vivo. Public databased and bioinformatics analysis were performed to screen the downstream molecules and determine the expression of MCM2 in cancers. KNTC1 was overexpressed in OS tissues and positively correlated with overall survival of OS patients. KNTC1 knockdown inhibited the proliferation and migration, and arrested G2 phase, and induced apoptosis. Besides, KNTC1 downregulation restricted the xenograft tumor formation. MCM2, one of the coexpressed genes, was highly expressed in sarcoma and downregulated after KNTC1 knockdown. MCM2 overexpression heightened the proliferation and migration ability of OS cells, which was reversed the inhibiting effects of KNTC1 knockdown. KNTC1 was overexpressed in OS and promoted the progression of OS by upregulating MCM2.

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Section: Discussionmentioning

confidence: 99%

KNTC1 knockdown inhibits the proliferation and migration of osteosarcoma cells by MCM2

Zhong,

Dong,

Liu

2024

Molecular Carcinogenesis

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“…Building cell models from 2nd to 6th generation cells. To induce hypoxic injury, HUVECs were exposed to low oxygen-containing gas (94% N 2 , 5% CO 2 , and 1% O 2 ) for 24 h, as previously reported [ 24 ]. The cells were split into five groups: normal, control (NC), hypoxic (hypoxic) (94% N 2 , 5% CO 2 , 1% O 2 , 24 h), hypoxic + hydrogen (95% N 2 , 4% CO 2 , 1% O 2 , 24 h + H 2 , 2 h), and hypoxic + hydrogen with Nrf2 inhibition (hypoxia + H 2 + ML385) (95% N 2 , 4% CO 2 , 1% O 2 , 24 h + H 2 , 2 h + ML385 2 μm, 24 h) (Selleck, Shanghai, China).…”

Section: Methodsmentioning

confidence: 99%

Molecular hydrogen promotes retinal vascular regeneration and attenuates neovascularization and neuroglial dysfunction in oxygen-induced retinopathy mice

Guo,

Qin,

Sun

et al. 2024

Biol Res

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Background Retinopathy of Prematurity (ROP) is a proliferative retinal vascular disease occurring in the retina of premature infants and is the main cause of childhood blindness. Nowadays anti-VEGF and retinal photocoagulation are mainstream treatments for ROP, but they develop a variety of complications. Hydrogen (H2) is widely considered as a useful neuroprotective and antioxidative therapeutic method for hypoxic-ischemic disease without toxic effects. However, whether H2 provides physiological angiogenesis promotion, neovascularization suppression and glial protection in the progression of ROP is largely unknown.This study aims to investigate the effects of H2 on retinal angiogenesis, neovascularization and neuroglial dysfunction in the retinas of oxygen-induced retinopathy (OIR) mice. Methods In this study, mice that were seven days old and either wild-type (WT) or Nrf2-deficient (Nrf2−/−) were exposed to 75% oxygen for 5 days and then returned to normal air conditions. Different stages of hydrogen gas (H2) inhalation were administered. Vascular obliteration, neovascularization, and blood vessel leakage were analyzed and compared. To count the number of neovascularization endothelial nuclei, routine HE staining of retinal sections was conducted. Immunohistochemistry was performed using DyLight 594 labeled GSL I-isolectin B4 (IB4), as well as primary antibodies against proliferating cell nuclear antigen (PCNA), glial fibrillary acidic protein (GFAP), and Iba-1. Western blots were used to measure the expression of NF-E2-related factor 2 (Nrf2), vascular endothelial growth factor (VEGF), Notch1, Dll4, and HIF-1α. Additionally, the expression of target genes such as NQO1, HO-1, Notch1, Hey1, Hey2, and Dll4 was measured. Human umbilical vein endothelial cells (HUVECs) treated with H2 under hypoxia were used as an in vitro model. RT-PCR was used to evaluate the mRNA expression of Nrf2, Notch/Dll4, and the target genes. The expression of reactive oxygen species (ROS) was observed using immunofluorescence staining. Results Our results indicate that 3–4% H2 does not disturb retinal physiological angiogenesis, but ameliorates vaso-obliteration and neovascularization in OIR mice. Moreover, H2 prevents the decreased density and reverses the morphologic and functional changes in retinal astrocytes caused by oxygen-induced injury. In addition, H2 inhalation reduces microglial activation, especially in the area of neovascularization in OIR mice. H2 plays a protective role in vascular regeneration by promoting Nrf2 activation and suppressing the Dll4-induced Notch signaling pathway in vivo. Also, H2 promotes the proliferation of HUVECs under hypoxia by negatively regulating the Dll4/Notch pathway and reducing ROS levels through Nrf2 pathway aligning with our findings in vivo.Moreover, the retinal oxygen-sensing mechanisms (HIF-1α/VEGF) are also involved in hydrogen-mediated retinal revascularization and neovascularization suppression. Conclusions Collectively, our results indicate that H2 could be a promising therapeutic agent for POR treatment and that its beneficial effect in human ROP might involve the activation of the Nrf2-Notch axis as well as HIF-1α/VEGF pathways. Graphical Abstract

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MicroRNA-based interventions in aberrant cell cycle diseases: Therapeutic strategies for cancers, central nervous system disorders and comorbidities

Tang,

Ren,

Zeng

et al. 2024

Biomedicine & Pharmacotherapy

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Hypoxia Inhibits Cell Cycle Progression and Cell Proliferation in Brain Microvascular Endothelial Cells via the miR-212-3p/MCM2 Axis

Cited by 5 publications

References 56 publications

KNTC1 knockdown inhibits the proliferation and migration of osteosarcoma cells by MCM2

KNTC1 knockdown inhibits the proliferation and migration of osteosarcoma cells by MCM2

Molecular hydrogen promotes retinal vascular regeneration and attenuates neovascularization and neuroglial dysfunction in oxygen-induced retinopathy mice

MicroRNA-based interventions in aberrant cell cycle diseases: Therapeutic strategies for cancers, central nervous system disorders and comorbidities

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