scholarly journals Transcriptional regulation of adrenomedullin by oncostatin M in human astroglioma cells: Implications for tumor invasion and migration

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Seul Ye Lim ◽  
So-Hee Ahn ◽  
Hyunju Park ◽  
Jungsul Lee ◽  
Kyungsun Choi ◽  
...  
2019 ◽  
Vol 120 (7) ◽  
pp. 11172-11189 ◽  
Author(s):  
Jiali Sun ◽  
Guoxin Ji ◽  
Jie Xie ◽  
Zhi Jiao ◽  
Haozheng Zhang ◽  
...  

2013 ◽  
Vol 35 (2) ◽  
pp. 469-478 ◽  
Author(s):  
Lin-Zi Li ◽  
Chris Zhiyi Zhang ◽  
Li-Li Liu ◽  
Chun Yi ◽  
Shi-Xun Lu ◽  
...  

2020 ◽  
Author(s):  
Maolin Tian ◽  
Gang Li ◽  
Bin Jiang ◽  
Sadula Abuduhaibaier ◽  
Dianrong Xiu ◽  
...  

Abstract Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Recent evidence indicates that circular RNAs (circRNAs) play important roles in tissue development, gene regulation, and carcinogenesis. However, whether circRNAs are involved in HCC progression and encode functional proteins remains largely unknown.Methods: Circular RNA microarrays were performed using three pathologically diagnosed HCC samples and their paired adjacent normal liver tissues. Cell invasion, migration, cell cycle, and apoptosis after circRNA overexpression were measured using a transwell culture system, a wound healing assay, and flow cytometry . Full-length, mutated, and truncated sequences of circEPS15 with a FLAG tag were inserted inside a circular expression vector. Western blotting was used to confirm circEPS15 expression and the requirement of internal ribosomal entry site (IRES) elements within the circRNA. The miRNA and mRNA expression profiles were obtained by analyzing data retrieved from The Cancer Genome Atlas (TCGA) database. We then constructed a ceRNA network of mRNAs, miRNAs, and circEPS15. Using tissue samples from own patients, we also verified certain analytical results with quantitative real-time PCR (qRT-PCR).Results: The expression of circEPS15 was downregulated in HCC tissues, and the survival curves showed that low circEPS15 levels were associated with poor overall survival in HCC patients. Overexpression of circEPS15 suppressed tumor invasion and migration by inhibiting the TJP1/CDH2/VIM signaling pathway and retarded cell cycle progression, but it had no effect on cell apoptosis. ceRNA analysis and qRT-PCR showed that there might be a circRNA (circEPS15)-miRNA (miR-24-3p)-mRNA (CIDEA) network in HCC. The spanning junction open reading frame in circEPS15 driven by IRES encoded a novel protein.Conclusions: Endogenous circEPS15 plays a novel role in repressing HCC through the ceRNA network and encoding a functional protein.


2021 ◽  
Author(s):  
Maolin Tian ◽  
Gang Li ◽  
Bin Jiang ◽  
Abuduhaibaier Sadula ◽  
Dianrong Xiu ◽  
...  

Abstract BackgroundHepatocellular carcinoma (HCC) is one kind of the leading causes of cancer-related deaths in the world. Recent evidence indicates that circular RNAs (circRNAs) play important roles in tissue development, gene transcription, signal regulation and tumorigenesis. However, whether circRNAs are involved in HCC progression and encode functional proteins remains largely unknown.MethodscircRNAs microarrays wereperformed using three pathologically diagnosed HCC samples and their paired adjacent normal liver tissues. Cell invasion, migration, cycle, and apoptosis post circRNA overexpression were measured using a transwell culture system, a wound healing assay, and flow cytometry. Full-length, mutated, and truncated sequences of circEPS15 with a FLAG tag were inserted into a circular expression vector. Western blotting was used to confirm circEPS15 expression and the requirement of internal ribosomal entry site (IRES) elements within the circRNA. The miRNA and mRNA expression profiles were obtained by analyzing data retrieved from The Cancer Genome Atlas (TCGA) database. We then constructed a ceRNA network ofcircEPS15, miRNAs, and mRNAs. ResultsThe expression of circEPS15 was downregulated in HCC tissues, and the survival curves showed that low circEPS15 levels were associated with poor overall survival in HCC patients. Overexpression of circEPS15 suppressed tumor invasion and migration by inhibiting the TJP1/CDH2/VIM signaling pathway and retarded cell cycle progression, yet had no effect on cell apoptosis. ceRNA analysis and qRT-PCR results suggest a possible circRNA (circEPS15)-miRNA (miR-24-3p)-mRNA (CIDEA) network in HCC. The spanning junction open reading frame in circEPS15 driven by IRES encoded a novel protein.ConclusionsEndogenous circEPS15 plays a novel role in repressing HCC through the ceRNA network and encoding a functional protein.


2017 ◽  
Vol 39 (12) ◽  
pp. 1827-1834 ◽  
Author(s):  
Yubing Wu ◽  
Jingnan Zhang ◽  
Shizhen Hou ◽  
Ziming Cheng ◽  
Maoxi Yuan

2014 ◽  
Vol 54 (10) ◽  
pp. 1159-1171 ◽  
Author(s):  
Tian Huanna ◽  
Zuo Tao ◽  
Wang Xiangfei ◽  
An Longfei ◽  
Xie Yuanyuan ◽  
...  

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769592 ◽  
Author(s):  
Goparaju Chandrika ◽  
Kumar Natesh ◽  
Deepak Ranade ◽  
Ashish Chugh ◽  
Padma Shastry

The phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin signaling pathway is crucial for tumor survival, proliferation, and progression, making it an attractive target for therapeutic intervention. In glioblastoma, activated mammalian target of rapamycin promotes invasive phenotype and correlates with poor patient survival. A wide range of mammalian target of rapamycin inhibitors are currently being evaluated for cytotoxicity and anti-proliferative activity in various tumor types but are not explored sufficiently for controlling tumor invasion and recurrence. We recently reported that mammalian target of rapamycin inhibitors—rapamycin, temsirolimus, torin 1, and PP242—suppressed invasion and migration promoted by tumor necrosis factor-alpha and phorbol-myristate-acetate in glioblastoma cells. As aggressive invasion and migration of tumors are associated with mesenchymal and stem-like cell properties, this study aimed to examine the effect of mammalian target of rapamycin inhibitors on these features in glioblastoma cells. We demonstrate that temsirolimus and torin 1 effectively reduced the constitutive as well as phorbol-myristate-acetate/oncostatin-M-induced expression of mesenchymal markers (fibronectin, vimentin, and YKL40) and neural stem cell markers (Sox2, Oct4, nestin, and mushashi1). The inhibitors significantly abrogated the neurosphere-forming capacity induced by phorbol-myristate-acetate and oncostatin-M. Furthermore, we demonstrate that the drugs dephosphorylated signal transducer and activator transcription factor 3, a major regulator of mesenchymal and neural stem cell markers implicating the role of signal transducer and activator transcription factor 3 in the inhibitory action of these drugs. The findings demonstrate the potential of mammalian target of rapamycin inhibitors as “stemness-inhibiting drugs” and a promising therapeutic approach to target glioma stem cells.


2018 ◽  
Vol 115 (33) ◽  
pp. E7786-E7794 ◽  
Author(s):  
Whitney R. Grither ◽  
Gregory D. Longmore

The action of the collagen binding receptor tyrosine kinase (RTK) discoidin domain receptor 2 (DDR2) in both tumor and tumor stromal cells has been established as critical for breast cancer metastasis. Small molecule inhibitors that target the extracellular domain of RTKs are rare, as they have classically been regarded as too small to block binding with large polypeptide ligands. Here, we report the identification and characterization of a selective, extracellularly acting small molecule inhibitor (WRG-28) of DDR2 that uniquely inhibits receptor–ligand interactions via allosteric modulation of the receptor. By targeting DDR2, WRG-28 inhibits tumor invasion and migration, as well as tumor-supporting roles of the stroma, and inhibits metastatic breast tumor cell colonization in the lungs. These findings represent an approach to inhibiting tumor–stromal interactions and support the development of allosteric inhibitors of DDR2, such as WRG-28, as a promising approach to antimetastasis treatment.


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