TRA2A promotes proliferation, migration, invasion and epithelial mesenchymal transition of glioma cells

Tan, Ying; Hu, Xi; Deng, Yongbing; Yuan, Peng; Xie, Yizhen; Wang, Jia

doi:10.1016/j.brainresbull.2018.10.006

Cited by 17 publications

(15 citation statements)

References 16 publications

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“…Little is known about TRA2A protein. It was first identified in insects together with its paralog TRA2B, which has been studied to a greater extent (Tan et al, 2018 ). It has been found that TRA2A can promote paclitaxel therapy and promote cancer progression in triple-negative breast cancers (Liu et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

In-Depth Bioinformatic Analyses of Nidovirales Including Human SARS-CoV-2, SARS-CoV, MERS-CoV Viruses Suggest Important Roles of Non-canonical Nucleic Acid Structures in Their Lifecycles

et al. 2020

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Non-canonical nucleic acid structures play important roles in the regulation of molecular processes. Considering the importance of the ongoing coronavirus crisis, we decided to evaluate genomes of all coronaviruses sequenced to date (stated more broadly, the order Nidovirales) to determine if they contain non-canonical nucleic acid structures. We discovered much evidence of putative G-quadruplex sites and even much more of inverted repeats (IRs) loci, which in fact are ubiquitous along the whole genomic sequence and indicate a possible mechanism for genomic RNA packaging. The most notable enrichment of IRs was found inside 5 ′ UTR for IRs of size 12+ nucleotides, and the most notable enrichment of putative quadruplex sites (PQSs) was located before 3 ′ UTR, inside 5 ′ UTR, and before mRNA. This indicates crucial regulatory roles for both IRs and PQSs. Moreover, we found multiple G-quadruplex binding motifs in human proteins having potential for binding of SARS-CoV-2 RNA. Non-canonical nucleic acids structures in Nidovirales and in novel SARS-CoV-2 are therefore promising druggable structures that can be targeted and utilized in the future.

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Section: Discussionmentioning

confidence: 99%

In-Depth Bioinformatic Analyses of Nidovirales Including Human SARS-CoV-2, SARS-CoV, MERS-CoV Viruses Suggest Important Roles of Non-canonical Nucleic Acid Structures in Their Lifecycles

et al. 2020

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“…promotes chemotherapy drugs resistance and tumor progression in triple-negative breast cancers via regulating alternative splicing [13] . TRA2A is highly expressed in glioma and promotes malignant biological behavior of glioma [14] . Additionally, RBPs mediated regulation of vascular function involves with long non-coding RNAs (lncRNAs) [15] .…”

Section: Abstract Blood Brain Barrier Alzheimer's Disease Tra2a LImentioning

confidence: 99%

TRA2A-induced upregulation of LINC00662 regulates blood-brain barrier permeability by affecting ELK4 mRNA stability in Alzheimer’s microenvironment

et al. 2020

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The blood-brain barrier (BBB) plays a pivotal role in maintenance and regulation of the neural microenvironment. The occurrence of BBB disruption is the pathological change of early Alzheimer's disease (AD). RNA-binding proteins and long non-coding RNAs are involved in the regulation of BBB permeability. Our study was performed to demonstrate TRA2A/LINC00662/ELK4 axis in regulating BBB permeability in AD microenvironment. In Aβ1-42-incubated microvascular endothelial cells (ECs) of BBB model in vitro, TRA2A and LINC00662 were enriched. TRA2A increased the stability of LINC00662 by binding with it. The knockdown of either TRA2A or LINC00662 decreased the BBB permeability via upregulating the expressions of tight junction-related proteins. ELK4 was lower expressed in BBB model in vitro in AD microenvironment. LINC00662 mediated the degradation of ELK4 mRNA by SMD pathway. The downregulated ELK4 increased the permeability of BTB by increasing the tight junctionrelated proteins expressions. TRA2A/LINC00662/ELK4 axis plays a crucial role in the regulation of BBB permeability in AD microenvironment, which may provide a novel target for the therapy of AD.

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“…The process of EMT is commonly characterized by downregulation of E-cad, a key epithelial marker, accompanied by upregulation of N-cad, Vimentin and Slug, which are crucial mesenchymal marker genes (19,37). compelling evidence has indicated that the 4 glioma cell lines (U251, SHG44, LN229 and T98G) used in the present study display different mesenchymal and epithelial characteristics and U251 cells expressed particularly low levels, but SHG44 cells displayed the highest levels of epithelial markers (38)(39)(40)(41). Additionally, SHG44 cells demonstrated the lowest levels, but LN229 cells exhibited the highest levels of mesenchymal markers (39).…”

Section: Discussionmentioning

confidence: 64%

Microrchidia family CW‑type zinc finger 2 promotes the proliferation, invasion, migration and epithelial‑mesenchymal transition of glioma by regulating PTEN/PI3K/AKT signaling via binding to N‑myc downstream regulated gene 1 promoter

et al. 2021

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Glioma is a common malignant tumor of the central nervous system with high incidence and mortality. The present study aimed to investigate the role of Microrchidia family CW-type zinc finger 2 (MORC2) in the development of glioma. Firstly, MORc2 expression was detected in several glioma cell lines (U251, SHG44, LN229 and T98G). Following MORC2 silencing, cell proliferation was evaluated using the cell Counting Kit-8 assay and the expression of proliferation-related proteins was assessed via immunofluorescence staining or western blotting. cell invasion and migration were assessed using transwell and wound healing assays, respectively. Western blotting and immunofluorescence staining were employed to determine the expression of epithelial-mesenchymal transition (EMT)-associated proteins. The protein expression of N-myc downstream regulated gene 1 (NDRG1) and PTEN/PI3K/AKT signaling was determined with western blot analysis. Then, the luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were employed to evaluate the binding between MORC2 and NDRG1 promoter. Subsequently, cellular functional experiments were performed to assess the effects of NdRG1 on the progression of glioma after NdRG1 and MORc2 overexpression. In addition, tumor-bearing experiments were conducted using a U251 tumor-bearing nude mice model to detect tumor growth. The expression of proliferation (proliferating cell nuclear antigen, cyclin-dependent kinase 2 and cyclin E1), migration [matrix metalloproteinase (MMP)2 and MMP9], EMT (E-cadherin, N-cadherin and Vimentin) and PTEN/PI3K/AKT signaling proteins in tumor tissues was examined with immunohistochemistry assay or western blotting. Results revealed that MORc2 was notably unregulated in glioma cells compared with the normal human astrocyte. Loss-function of MORc2 inhibited the proliferation, invasion, migration and EMT of glioma cells. Importantly, MORc2 silencing upregulated NdRG1 expression and inactivated PTEN/PI3K/AKT signaling. Additionally, the luciferase reporter-and ChIP assays confirmed that MORC2 could bind to the NdRG1 promoter. NdRG1 upregulation suppressed the progression of glioma and these effects were partially reversed by MORc2 overexpression. Results of tumor-bearing experiments suggested that gain-function of NdRG1 inhibited tumor growth and downregulated the expression of proliferation, migration and EMT-related proteins in tumorous tissue in U251 tumor-bearing mice, which was partially counteracted after MORc2 overexpression. In addition, MORc2 overexpression abrogated the inhibitory effect of NdRG1 on PTEN/PI3K/AKT signaling. In summary, MORC2 promoted the progression of glioma by inactivation of PTEN/PI3K/AKT signaling via binding to NdRG1 promoter, providing a novel and potent target for the treatment of glioma.

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TRA2A promotes proliferation, migration, invasion and epithelial mesenchymal transition of glioma cells

Cited by 17 publications

References 16 publications

In-Depth Bioinformatic Analyses of Nidovirales Including Human SARS-CoV-2, SARS-CoV, MERS-CoV Viruses Suggest Important Roles of Non-canonical Nucleic Acid Structures in Their Lifecycles

In-Depth Bioinformatic Analyses of Nidovirales Including Human SARS-CoV-2, SARS-CoV, MERS-CoV Viruses Suggest Important Roles of Non-canonical Nucleic Acid Structures in Their Lifecycles

TRA2A-induced upregulation of LINC00662 regulates blood-brain barrier permeability by affecting ELK4 mRNA stability in Alzheimer’s microenvironment

Microrchidia family CW‑type zinc finger 2 promotes the proliferation, invasion, migration and epithelial‑mesenchymal transition of glioma by regulating PTEN/PI3K/AKT signaling via binding to N‑myc downstream regulated gene 1 promoter

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