MicroRNA-433 Inhibits the Proliferation and Migration of HUVECs and Neurons by Targeting Hypoxia-Inducible Factor 1 Alpha

2016 ◽  
Vol 61 (2) ◽  
pp. 135-143 ◽  
Author(s):  
Lin Zhang ◽  
Yuanxiao Zhang ◽  
Xiaohua Zhang ◽  
Yan Zhang ◽  
Yi Jiang ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1 ◽  
And Migration ◽  
Proliferation And Migration

scholarly journals HIF-1-miR-219-SMC4 Regulatory Pathway Promoting Proliferation and Migration of HCC under Hypoxic Condition

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Yang Chen ◽  
Fei Huang ◽  
liang Deng ◽  
Xiaowei Yuan ◽  
Qiang Tao ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Hypoxia Inducible Factor ◽  
Hypoxic Condition ◽  
Regulatory Pathway ◽  
Mesenchymal Transition ◽  
Hypoxia Inducible Factor 1 ◽  
Structural Maintenance Of Chromosome ◽  
And Migration ◽  
Hcc Cells ◽  
Proliferation And Migration

This paper aims to investigate the function of structural maintenance of chromosome 4 (SMC4) in the progression of hepatocellular carcinoma (HCC) under hypoxic condition. In this study, we found that suppression of SMC4 could inhibit proliferation and migration of HCC cells through inducing G1 phase arrest and affecting process of epithelial-mesenchymal transition (EMT) under hypoxic condition. Moreover, we demonstrated that SMC4 was transcriptionally regulated by hypoxia-inducible factor-1 (HIF-1) under hypoxic condition. As SMC has been shown to be a target gene of miR-219, we observed that miR-219 was downregulated under hypoxic condition and suppression of HIF-1a could lead to the upregulation of miR-219. We also proved that miR-219 could affect the proliferation and migration of HCC cells under hypoxic condition. In conclusion, our study demonstrated a novel HIF-1-miR-219-SMC4 regulatory pathway under hypoxic condition in HCC cells.

scholarly journals MiRNA let-7b promotes the development of hypoxic pulmonary hypertension by targeting ACE2

2019 ◽  
Vol 316 (3) ◽  
pp. L547-L557 ◽  
Author(s):  
Ruifeng Zhang ◽  
Hua Su ◽  
Xiuqing Ma ◽  
Xiaoling Xu ◽  
Li Liang ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Hypoxia Inducible Factor ◽  
Underlying Mechanism ◽  
Pulmonary Vessel ◽  
Hypoxic Pulmonary Hypertension ◽  
And Migration ◽  
Ventricle Hypertrophy ◽  
Proliferation And Migration

Angiotensin-converting enzyme 2 (ACE2) protects against hypoxic pulmonary hypertension (HPH) by inhibiting the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs). Under hypoxia, the hypoxia-inducible factor 1α (HIF-1α) inhibits ACE2 indirectly; however, the underlying mechanism is unclear. In the present study, we found that exposure to chronic hypoxia stimulated microRNA (miRNA) let-7b expression in rat lung via a HIF-1α-dependent pathway. Let-7b downregulated ACE2 expression by directly targeting the coding sequence of ACE2. Our in vitro and in vivo results revealed that let-7b contributed to the pathogenesis of HPH by inducing PASMCs proliferation and migration. Let-7b knockout mitigated right ventricle hypertrophy and pulmonary vessel remodeling in HPH by restoring ACE2 expression. Overall, we demonstrated that HIF-1α inhibited ACE2 expression via the HIF-1α-let-7b-ACE2 axis, which contributed to the pathogenesis of HPH by stimulating PASMCs proliferation and migration. Since let-7b knockout alleviated the development of HPH, let-7b may serve as a potential clinical target for the treatment of HPH.

Role of hypoxia-inducible factor-1α as a cancer therapy target

2006 ◽  
Vol 13 (Supplement_1) ◽  
pp. S61-S75 ◽  
Author(s):  
Shalini Patiar ◽  
Adrian L Harris
Keyword(s):  
Anticancer Agents ◽  
Ph Regulation ◽  
Hypoxia Inducible Factor ◽  
Genetic Alterations ◽  
Solid Tumours ◽  
Tumour Suppressor Genes ◽  
Hypoxia Inducible Factor 1 ◽  
And Migration ◽  
Patient Prognosis ◽  
Therapy Target

Hypoxia occurs in solid tumours due to a mismatch between tumour growth and angiogenesis. Hypoxia in solid tumours is associated with an aggressive phenotype and resistance to radiation therapy and chemotherapy leading to poor patient prognosis. Hypoxia-inducible factor-1 (HIF-1) is a transcription factor, which is activated in response to intratumoural hypoxia and as a result of genetic alterations that activate oncogenes and inactivate tumour suppressor genes. It plays a key role in the adaptation of tumour cells to hypoxia by activating the transcription of genes, which regulate several biological processes including angiogenesis, cell proliferation and survival, glucose metabolism, pH regulation and migration. This makes HIF-1 an attractive target for the development of anticancer agents. The success of these agents depends on reliable methods to identify those patients most likely to benefit from HIF-1-targeted therapy. Several novel small molecule inhibitors of HIF-1 have been identified and are moving towards clinical trials, but none of these are specific for HIF-1. Further work is ongoing to identify more selective HIF-1 inhibitors.

scholarly journals PDK1 regulation of mTOR and hypoxia-inducible factor 1 integrate metabolism and migration of CD8+T cells

2012 ◽  
Vol 199 (6) ◽  
pp. i8-i8 ◽  
Author(s):  
David K. Finlay ◽  
Ella Rosenzweig ◽  
Linda V. Sinclair ◽  
Carmen Feijoo-Carnero ◽  
Jens L. Hukelmann ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1 ◽  
And Migration

Role of HIF-1α in the regulation ACE and ACE2 expression in hypoxic human pulmonary artery smooth muscle cells

2009 ◽  
Vol 297 (4) ◽  
pp. L631-L640 ◽  
Author(s):  
Ruifeng Zhang ◽  
Yingli Wu ◽  
Meng Zhao ◽  
Chuanxu Liu ◽  
Lin Zhou ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Smooth Muscle Cells ◽  
Hypoxia Inducible Factor ◽  
Muscle Cells ◽  
Underlying Mechanism ◽  
Transcriptional Level ◽  
Pulmonary Artery Smooth Muscle ◽  
And Migration ◽  
Proliferation And Migration

Angiotensin-converting enzyme (ACE) enhances the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs), which contribute to the pathogenesis of hypoxic pulmonary hypertension (HPH). Previous reports have demonstrated that hypoxia upregulates ACE expression, but the underlying mechanism is unknown. Here, we found that ACE is persistently upregulated in PASMCs on the transcriptional level during hypoxia. Hypoxia-inducible factor 1α (HIF-1α), a key transcription factor activated during hypoxia, was able to upregulate ACE protein expression under normoxia, whereas knockdown of HIF-1α expression in PASMCs inhibited hypoxia-induced ACE upregulation. Furthermore, HIF-1α can bind and transactivate the ACE promoter directly. Therefore, we report that ACE is a novel target of HIF-1α. Recently, a homolog of ACE, ACE2, was reported to counterbalance the function of ACE. In contrast to ACE, we found that ACE2 mRNA and protein levels increased during the early stages of hypoxia and decreased to near-baseline levels at the later stages after HIF-1α accumulation. Thus HIF-1α inhibited ACE2 expression, and the accumulated ANG II catalyzed by ACE is a key mediator in the downregulation of ACE2 by HIF-1α. Moreover, a reduction of ACE2 expression in PASMCs by RNA interference was accompanied by significantly enhanced proliferation and migration during hypoxia. We conclude that ACE is directly regulated by HIF-1α, whereas ACE2 is regulated in a bidirectional way during hypoxia and may play a protective role during the development of HPH. In sum, these findings contribute to the understanding of the pathogenesis of HPH.

scholarly journals Inhalational Anesthetics Inhibit Neuroglioma CellProliferation and Migration via miR-138, -210 and -335

2021 ◽  
Vol 22 (9) ◽  
pp. 4355
Author(s):  
Masashi Ishikawa ◽  
Masae Iwasaki ◽  
Hailin Zhao ◽  
Junichi Saito ◽  
Cong Hu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Glioma Cell ◽  
Hypoxia Inducible Factor ◽  
Immunofluorescent Staining ◽  
Inhalational Anesthetics ◽  
Cell Proliferation And Migration ◽  
Underlying Mechanisms ◽  
And Migration ◽  
Proliferation And Migration ◽  
Cell Malignancy

Inhalational anesthetics was previously reported to suppress glioma cell malignancy but underlying mechanisms remain unclear. The present study aims to investigate the effects of sevoflurane and desflurane on glioma cell malignancy changes via microRNA (miRNA) modulation. The cultured H4 cells were exposed to 3.6% sevoflurane or 10.3% desflurane for 2 h. The miR-138, -210 and -335 expression were determined with qRT-PCR. Cell proliferation and migration were assessed with wound healing assay, Ki67 staining and cell count kit 8 (CCK8) assay with/without miR-138/-210/-335 inhibitor transfections. The miRNA downstream proteins, hypoxia inducible factor-1α (HIF-1α) and matrix metalloproteinase 9 (MMP9), were also determined with immunofluorescent staining. Sevoflurane and desflurane exposure to glioma cells inhibited their proliferation and migration. Sevoflurane exposure increased miR-210 expression whereas desflurane exposure upregulated both miR-138 and miR-335 expressions. The administration of inhibitor of miR-138, -210 or -335 inhibited the suppressing effects of sevoflurane or desflurane on cell proliferation and migration, in line with the HIF-1α and MMP9 expression changes. These data indicated that inhalational anesthetics, sevoflurane and desflurane, inhibited glioma cell malignancy via miRNAs upregulation and their downstream effectors, HIF-1α and MMP9, downregulation. The implication of the current study warrants further study.

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