ZEB1-activated LINC01123 accelerates the malignancy in lung adenocarcinoma through NOTCH signaling pathway

AbstractGrowing incidence of lung adenocarcinoma (LUAD) has been detected recently. Multiple long non-coding RNAs (lncRNAs) have been proven as tumor facilitators or inhibitors by extensive works. Present study concentrated on characterizing the potential role of LINC01123 in LUAD. We explored the differential expression of LINC01123 through qRT-PCR and found the amplification of LINC01123 in LUAD cell lines. It was ascertained that LINC01123 was definitely responsible for the malignant processes of LUAD cells. Further, we validated the ceRNA network of LINC01123/miR-449b-5p/NOTCH1 in LUAD via mechanical experiments. As a transcriptional factor related to epithelial mesenchymal transition (EMT), ZEB1 was responsible for the transcriptional activation of both LINC01123 and NOTCH1. The involvement of NOTCH signaling in LUAD was interrogated through evaluating functional changes after treating with FLI-06 (NOTCH pathway suppressor). It showed that FLI-06-caused NOTCH signaling inactivation suppressed malignant functions in LUAD cells. Additionally, LINC01123 facilitated NOTCH1-dependent NOTCH signaling activation. Rescue experiments probed the modulatory function of LINC01123/miR-449b-5p/NOTCH1 in LUAD cellular processes. Altogether, ZEB1-activated LINC01123 accelerates the malignancy in LUAD through miR-449b-5p/NOTCH1 axis-mediated NOTCH signaling pathway, while NOTCH1 boosts ZEB1 in return. These observations suggest the huge potential of LINC01123 as a new target for LUAD therapy.

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JAG1, Regulated by microRNA-424-3p, Involved in Tumorigenesis and Epithelial–Mesenchymal Transition of High Proliferative Potential-Pituitary Adenomas

Frontiers in Oncology ◽

10.3389/fonc.2020.567021 ◽

2020 ◽

Vol 10 ◽

Author(s):

Yiyuan Chen ◽

Bin Li ◽

Jie Feng ◽

Qiuyue Fang ◽

Jianhua Cheng ◽

...

Keyword(s):

Cell Proliferation ◽

Notch Signaling ◽

Cell Line ◽

Signaling Pathway ◽

Pituitary Adenomas ◽

Epithelial Mesenchymal Transition ◽

Notch Pathway ◽

Notch Signaling Pathway ◽

Mesenchymal Transition ◽

Gh3 Cell

Pituitary adenomas (PAs) are a neoplastic proliferation of anterior pituitary. Signature of Notch pathway relies upon the histopathological type of PAs. The details of Notch pathway that are involved in the migration and invasion of Pas are still unclear. This paper filters and testifies the relation between Notch signaling pathway and the migration/invasion in subtypes of PAs. The diversity of genes and pathways is investigated based on transcriptome data of 60 patients by KEGG pathway analysis and GSEA. A series of functional experiments demonstrate the role of candidate genes by overexpression and antibody blocking in GH3 cell line. Volcano map and GSEA results exhibit the differential and the priority of Jagged1 canonical Notch Ligand (JAG1) in the Notch pathway combined with clinical features. JAG1 is involved in epithelial–mesenchymal transition (EMT) in PAs by correlation analysis of RNA-seq data. Progression-free survival (PFS) of patients with high JAG1 was shorter than patients with low JAG1 according to follow-up data (P = 0.006). Furthermore, overexpression and antibody blocking experiments in GH3 cell line indicate that JAG1 could promote cell proliferation, migration, and G1/S transition. Double luciferase reporter assay gives manifests that JAG1 is the target gene of miR-424-3p, and mimics or inhibitor of miR-424-3p can regulate the level of JAG1 which, in turn, affects cell proliferation and the levels of MMP2 and VIM in GH3 cell line, respectively. Our study delves into the relation between the Notch signaling pathway and cell proliferation and EMT in PAs, providing a potential treatment through targeting JAG1.

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MicroRNA-3163 targets ADAM-17 and enhances the sensitivity of hepatocellular carcinoma cells to molecular targeted agents

Cell Death and Disease ◽

10.1038/s41419-019-2023-1 ◽

2019 ◽

Vol 10 (10) ◽

Cited By ~ 7

Author(s):

Bin Yang ◽

Chunping Wang ◽

Hui Xie ◽

Yiwu Wang ◽

Jiagan Huang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Notch Signaling ◽

Signaling Pathway ◽

Epithelial Mesenchymal Transition ◽

Notch Signaling Pathway ◽

Advanced Hepatocellular Carcinoma ◽

Targeted Agents ◽

Mesenchymal Transition ◽

Molecular Targeted Agents ◽

Hcc Cells

Abstract Molecular targeted agents, such as sorafenib, remain the only choice of an antitumor drug for the treatment of advanced hepatocellular carcinoma (HCC). The Notch signaling pathway plays central roles in regulating the cellular injury/stress response, anti-apoptosis, or epithelial–mesenchymal transition process in HCC cells, and is a promising target for enhancing the sensitivity of HCC cells to antitumor agents. The ADAM metalloprotease domain-17 (ADAM-17) mediates the cleavage and activation of Notch protein. In the present study, microRNA-3163 (miR-3163), which binds to the 3′-untranslated region of ADAM-17, was screened using online methods. miRDB and pre-miR-3163 sequences were prepared into lentivirus particles to infect HCC cells. miR-3163 targeted ADAM-17 and inhibited the activation of the Notch signaling pathway. Infection of HCC cells with miR-3163 enhanced their sensitivity to molecular targeted agents, such as sorafenib. Therefore, miR-3163 may contribute to the development of more effective strategies for the treatment of advanced HCC.

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The Notch signalling pathway and breast cancer: The importance of balance and cellular self-control.

Current Signal Transduction Therapy ◽

10.2174/1574362414666190916120659 ◽

2019 ◽

Vol 14 ◽

Author(s):

Germán Saucedo-Correa ◽

Alejandro Bravo-Patiño ◽

Rosa Elvira Núñez-Anita ◽

Javier Oviedo-Boyso ◽

Juan José Valdez-Alarcón ◽

...

Keyword(s):

Notch Signaling ◽

Signaling Pathway ◽

Cross Talk ◽

Transcriptional Activation ◽

Notch Pathway ◽

Notch Signaling Pathway ◽

Self Control ◽

Design Strategies ◽

Notch Intracellular Domain ◽

The Cross

Notch is a cell-signaling pathway that is highly conserved in all metazoans and is responsible for cell differentiation and cross-talk communication with other signaling pathways such as WNT and Hh. In most cancers, the Notch signaling pathway is altered, causing atypical activity of vital processes such as cell cycle, differentiation and apoptosis, leading the cell to a carcinogenic state. Currently, the Notch signaling pathway has taken a special interest to design strategies in order to regulate the activity of this pathway since it is known that in the cancer molecular micro-environment the Notch pathway is over-expressed or presents an aberrant function, which, in consequence, corrupts the cross-talk communication with WNT and Hh pathways. Most of the existing strategies are focused on the systematic and whole inhibition of Notch pathway at the membrane level by the use of γ-secretases inhibitors. There are few strategies that act at the nuclear level inhibiting the activity of the transcriptional activation complex composed by the Notch intracellular domain, the transcriptional factor CSL and the Mastermind co-activator. In this review, by the fact that there are not any strategy focused to revert the over expression effect caused by the Notch pathway constitutive activity, we propose that the efforts to develop new strategies against cancer should be focused to understand the complexity of the cross-talk communication between Notch, WNT and Hh pathways to neutralize the gene aberrant activity characteristic of cancer cells which are responsible for those corrupted cross-talk communication.

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SATB1 promotes epithelial-mesenchymal transition via Notch signaling pathway in colorectal cancer

European Journal of Inflammation ◽

10.1177/2058739219858896 ◽

2019 ◽

Vol 17 ◽

pp. 205873921985889

Author(s):

Jun Tang ◽

Jingfang Yang

Keyword(s):

Colorectal Cancer ◽

Notch Signaling ◽

Signaling Pathway ◽

Epithelial Mesenchymal Transition ◽

Prognostic Biomarker ◽

Notch Signaling Pathway ◽

Vital Role ◽

Cell Models ◽

Mesenchymal Transition ◽

Promising Therapeutic Target

Epithelial-mesenchymal transition (EMT) is essential for initiation of colorectal cancer (CRC) metastasis, but the diver proteins of EMT remain unclear. Special AT-rich sequence-binding protein 1 (SATB1) was found to be overexpressed in CRC cell lines, and its expression level was positively correlated with CRC progression. Strikingly, EMT process was regulated by SATB1, as SATB1 overexpression upregulated E-cadherin and SATB1 knockdown inhibited N-cadherin cell models. Mechanistically, SATB1 promoted EMT-mediated CRC metastasis via activation of Notch signaling pathway. Taken together, SATB1 plays a vital role in CRC metastasis and may act as a novel prognostic biomarker and a promising therapeutic target for CRC.

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