Knockdown of long noncoding RNA MEG3 impairs VEGF-stimulated endothelial sprouting angiogenesis via modulating VEGFR2 expression in human umbilical vein endothelial cells

Ruan, Wenchen; Zhao, Feng; Zhao, Shouxun; Zhang, Luyong; Shi, Lei; Pang, Tao

doi:10.1016/j.gene.2018.01.072

Cited by 57 publications

(39 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…And downregulation of the MEG3 inhibits cell proliferation by repressing the NOTCH signaling pathway (Guo, Qian, Yan, Li, Huang, ). Moreover, knockdown of MEG3 impaired VEGF‐induced sprouting angiogenesis by modulating VEGFR2 expression (Ruan, Zhao, Zhao, & Shunyi, ). However, miR‐210 can also decrease VEGF‐A expression, leading to the damaged tube formation (Hua et al, ).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐210 regulates human trophoblast cell line HTR‐8/SVneo function by attenuating Notch1 expression: Implications for the role of microRNA‐210 in pre‐eclampsia

Wang

Liu

et al. 2019

Molecular Reproduction Devel

View full text Add to dashboard Cite

Successful pregnancy depends on the precise regulation of extravillous trophoblast cell invasion ability. MicroRNA‐210‐3p (miR‐210), which is increased in the placenta of pre‐eclampsia. Furthermore, miR‐210 could inhibit trophoblasts invasion and might act as a serum biomarker for pre‐eclampsia. Previous studies have demonstrated that miR‐210 regulates HUVEC (human umbilical vein endothelial cell)‐mediated angiogenesis by regulating the NOTCH1 signaling pathway. Studies by our group have previously identified that NOTCH1 plays a positive role in regulating trophoblast functions. However, the miR‐210/NOTCH1 signaling pathway in the regulation of trophoblasts and pre‐eclampsia has not been characterized. Therefore, this study was conducted to investigate the role of miR‐210 and its relationship with NOTCH1 in trophoblasts. We first examined the expression levels of miR‐210 and NOTCH1 in pre‐eclamptic and normals placentas. Next, the expression and location of miR‐210 and NOTCH1 in the first‐trimester villi, maternal decidua, and placenta of late pregnancy were shown via in situ hybridization and immunohistochemistry. The trophoblast cell line HTR‐8/SVneo was used to investigate the effects of miR‐210 on the expression of NOTCH1 and cell bioactivity by upregulation and downregulation strategies. The results showed that miR‐210 expression was increased, whereas NOTCH1 expression was decreased in pre‐eclamptic placenta compared with controls. Upregulation of miR‐210 decreased NOTCH1 expression, impaired HTR‐8/SVneo proliferation, migration, invasion, and tube‐like formation capabilities, and promoted apoptosis. In contrast, downregulation of miR‐210 resulted in the opposite effects. These findings suggested that miR‐210 might act as a contributor to trophoblast dysfunction by attenuating NOTCH1 expression.

show abstract

Section: Discussionmentioning

confidence: 99%

MicroRNA‐210 regulates human trophoblast cell line HTR‐8/SVneo function by attenuating Notch1 expression: Implications for the role of microRNA‐210 in pre‐eclampsia

Wang

Liu

et al. 2019

Molecular Reproduction Devel

View full text Add to dashboard Cite

show abstract

“…Several microRNAs (miRs) regulate MEG3, including miR-148a and miR-29 in cancer; the latter is regulated by the Hippo/ YAP pathway (46)(47)(48). Hypoxic conditions and HIF1α enhanced expression of MEG3 in human umbilical endothelial cells (49,50). Increased YAP activity (11) and hypoxemia may contribute to the increased expression of MEG3 in IPF epithelial cells (51,52).…”

Section: Discussionmentioning

confidence: 99%

MEG3 is increased in idiopathic pulmonary fibrosis and regulates epithelial cell differentiation

Gokey¹,

Snowball²,

Sridharan³

et al. 2018

JCI Insight

View full text Add to dashboard Cite

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease causing fibrotic remodeling of the peripheral lung, leading to respiratory failure. Peripheral pulmonary epithelial cells lose normal alveolar epithelial gene expression patterns and variably express genes associated with diverse conducting airway epithelial cells, including basal cells. Single-cell RNA sequencing of pulmonary epithelial cells isolated from IPF lung tissue demonstrated altered expression of LncRNAs, including increased MEG3. MEG3 RNA was highly expressed in subsets of the atypical IPF epithelial cells and correlated with conducting airway epithelial gene expression patterns. Expression of MEG3 in human pulmonary epithelial cell lines increased basal cell-associated RNAs, including TP63, KRT14, STAT3, and YAP1, and enhanced cell migration, consistent with a role for MEG3 in regulating basal cell identity. MEG3 reduced expression of TP73, SOX2, and Notch-associated RNAs HES1 and HEY1, in primary human bronchial epithelial cells, demonstrating a role for MEG3 in the inhibition of genes influencing basal cell differentiation into club, ciliated, or goblet cells. MEG3 induced basal cell genes and suppressed genes associated with terminal differentiation of airway cells, supporting a role for MEG3 in regulation of basal progenitor cell functions, which may contribute to tissue remodeling in IPF.

show abstract

“…Due to the inability of researchers to identify a HIF-1α binding motif in the MEG3 core promoter, Ruan et al speculated that HIF-1α activated lncRNA MEG3 in an indirect manner in human umbilical vein endothelial cells, in which CBP/p300 recruitment for cAMP responsive element binding protein 1 (CREB) transcriptional activation is also required [91]. Although HIF-1α itself can promote lncRNA H19 expression by interacting physically, the knowledge of a concurrent activation pathway of lncRNA H19 expression depending on the interaction between HIF-1α-induced SP1 and the H19 promoter in aggressive glioblastoma cells further expands existing understanding [92].…”

Section: Indirect Regulation Of Hrl Transcription By Hif-1αmentioning

confidence: 99%

The interplay between HIF-1α and noncoding RNAs in cancer

Peng

Han

et al. 2020

J Exp Clin Cancer Res

View full text Add to dashboard Cite

Hypoxia is a classic characteristic of the tumor microenvironment with a significant impact on cancer progression and therapeutic response. Hypoxia-inducible factor-1 alpha (HIF-1α), the most important transcriptional regulator in the response to hypoxia, has been demonstrated to significantly modulate hypoxic gene expression and signaling transduction networks. In past few decades, growing numbers of studies have revealed the importance of noncoding RNAs (ncRNAs) in hypoxic tumor regions. These hypoxia-responsive ncRNAs (HRNs) play pivotal roles in regulating hypoxic gene expression at the transcriptional, posttranscriptional, translational and posttranslational levels. In addition, as a significant gene expression regulator, ncRNAs exhibit promising roles in regulating HIF-1α expression at multiple levels. In this review, we briefly elucidate the reciprocal regulation between HIF-1α and ncRNAs, as well as their effect on cancer cell behaviors. We also try to summarize the complex feedback loop existing between these two components. Moreover, we evaluated the biomarker potential of HRNs for the diagnosis and prognosis of cancer, as well as the potential clinical utility of shared regulatory mechanisms between HIF-1α and ncRNAs in cancer treatment, providing novel insights into tumorigenicity, which may lead to innovative clinical applications.

show abstract

Knockdown of long noncoding RNA MEG3 impairs VEGF-stimulated endothelial sprouting angiogenesis via modulating VEGFR2 expression in human umbilical vein endothelial cells

Cited by 57 publications

References 24 publications

MicroRNA‐210 regulates human trophoblast cell line HTR‐8/SVneo function by attenuating Notch1 expression: Implications for the role of microRNA‐210 in pre‐eclampsia

MicroRNA‐210 regulates human trophoblast cell line HTR‐8/SVneo function by attenuating Notch1 expression: Implications for the role of microRNA‐210 in pre‐eclampsia

MEG3 is increased in idiopathic pulmonary fibrosis and regulates epithelial cell differentiation

The interplay between HIF-1α and noncoding RNAs in cancer

Contact Info

Product

Resources

About