CHEK1: a hub gene related to poor prognosis for lung adenocarcinoma

2021 ◽  
Author(s):  
Zhibo Tan ◽  
Min Chen ◽  
Ying Wang ◽  
Feng Peng ◽  
Xiaopeng Zhu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Poor Prognosis ◽  
Epithelial To Mesenchymal Transition ◽  
Gene Expression Omnibus ◽  
Intratumor Heterogeneity ◽  
Mirna Regulation ◽  
Hub Genes ◽  
Mesenchymal Transition ◽  
Expression Atlas ◽  
Human Protein Atlas

Aim: The study aims to pinpoint hub genes and investigate their functions in order to gain insightful understandings of lung adenocarcinoma (LUAD). Methods: Bioinformatic approaches were adopted to investigate genes in databases including Gene Expression Omnibus, WebGestalt, STRING and Cytoscape, GEPIA2, Oncomine, Human Protein Atlas, TIMER2.0, UALCAN, cBioPortal, TargetScanHuman, OncomiR, ENCORI, Kaplan–Meier plotter, UCSC Xena, European Molecular Biology Laboratory – European Bioinformatics Institute Single Cell Expression Atlas and CancerSEA. Results: Five hub genes were ascertained. CHEK1 was overexpressed in a range of cancers, including LUAD. Promoter methylation, amplification and miRNA regulation might trigger CHEK1 upregulation, signaling poor prognosis. CHEK1 with its coexpressed genes were enriched in the cell cycle pathway. Intratumor heterogeneity of CHEK1 expression could be observed. Cell clusters with CHEK1 expression were more prone to metastasis and epithelial-to-mesenchymal transition. Conclusion: CHEK1 might potentially act as a prognostic biomarker for LUAD.

KCNN4 promotes the progression of lung adenocarcinoma by activating the AKT and ERK signaling pathways

2021 ◽  
pp. 1-15
Author(s):  
Ping Xu ◽  
Xiao Mo ◽  
Ruixue Xia ◽  
Long Jiang ◽  
Chengfei Zhang ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Lung Adenocarcinoma ◽  
Potassium Channel ◽  
Signaling Pathways ◽  
Epithelial To Mesenchymal Transition ◽  
Tumor Biology ◽  
Erk Signaling ◽  
Mesenchymal Transition

BACKGROUND: Potassium channels, encoded by more than seventy genes, are cell excitability transmembrane proteins and become evident to play essential roles in tumor biology. OBJECTIVE: The deregulation of potassium channel genes has been related to cancer development and patient prognosis. The objective of this study is to understand the role of potassium channels in lung cancer. METHODS: We examined all potassium channel genes and identified that KCNN4 is the most significantly overexpressed one in lung adenocarcinoma. The role and mechanism of KCNN4 in lung adenocarcinoma were further investigated by in vitro cell and molecular assay and in vivo mouse xenograft models. RESULTS: We revealed that the silencing of KCNN4 significantly inhibits cell proliferation, migration, invasion, and tumorigenicity of lung adenocarcinoma. Further studies showed that knockdown of KCNN4 promotes cell apoptosis, induces cell cycle arrested in the S phase, and is associated with the epithelial to mesenchymal transition (EMT) process. Most importantly, we demonstrated that KCNN4 regulates the progression of lung adenocarcinoma through P13K/AKT and MEK/ERK signaling pathways. The use of inhibitors that targeted AKT and ERK also significantly inhibit the proliferation and metastasis of lung adenocarcinoma cells. CONCLUSIONS: This study investigated the function and mechanism of KCNN4 in lung adenocarcinoma. On this basis, this means that KCNN4 can be used as a tumor marker for lung adenocarcinoma and is expected to become an important target for a potential drug.

scholarly journals RUFY3 Predicts Poor Prognosis and Promotes Metastasis through Epithelial-mesenchymal Transition in Lung Adenocarcinoma

2019 ◽  
Vol 10 (25) ◽  
pp. 6278-6285 ◽  
Author(s):  
Wanfu Men ◽  
Wenya Li ◽  
Yu Li ◽  
Jungang Zhao ◽  
Xiaohan Qu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition

scholarly journals Jagged1-mediated Notch activation induces epithelial-to-mesenchymal transition through Slug-induced repression of E-cadherin

2007 ◽  
Vol 204 (12) ◽  
pp. 2935-2948 ◽  
Author(s):  
Kevin G. Leong ◽  
Kyle Niessen ◽  
Iva Kulic ◽  
Afshin Raouf ◽  
Connie Eaves ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Poor Prognosis ◽  
Epithelial To Mesenchymal Transition ◽  
Breast Tumors ◽  
Aberrant Expression ◽  
Mesenchymal Transition ◽  
Slug Expression ◽  
Tumor Growth And Metastasis ◽  
Notch Activation ◽  
E Cadherin

Aberrant expression of Jagged1 and Notch1 are associated with poor outcome in breast cancer. However, the reason that Jagged1 and/or Notch overexpression portends a poor prognosis is unknown. We identify Slug, a transcriptional repressor, as a novel Notch target and show that elevated levels of Slug correlate with increased expression of Jagged1 in various human cancers. Slug was essential for Notch-mediated repression of E-cadherin, which resulted in β-catenin activation and resistance to anoikis. Inhibition of ligand-induced Notch signaling in xenografted Slug-positive/E-cadherin–negative breast tumors promoted apoptosis and inhibited tumor growth and metastasis. This response was associated with down-regulated Slug expression, reexpression of E-cadherin, and suppression of active β-catenin. Our findings suggest that ligand-induced Notch activation, through the induction of Slug, promotes tumor growth and metastasis characterized by epithelial-to-mesenchymal transition and inhibition of anoikis.

scholarly journals Monoamine Oxidase B Expression Correlates with a Poor Prognosis in Colorectal Cancer Patients and Is Significantly Associated with Epithelial-to-Mesenchymal Transition-Related Gene Signatures

2020 ◽  
Vol 21 (8) ◽  
pp. 2813 ◽  
Author(s):  
Yi-Chieh Yang ◽  
Ming-Hsien Chien ◽  
Tsung-Ching Lai ◽  
Chia-Yi Su ◽  
Yi-Hua Jan ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Epithelial To Mesenchymal Transition ◽  
Disease Free Survival ◽  
In Silico Analysis ◽  
Tissue Microarrays ◽  
Disease Stage ◽  
Clinicopathological Parameters ◽  
Gene Expressions ◽  
Mesenchymal Transition ◽  
Colorectal Cancer Patients

Monoamine oxidases (MAOs) including MAOA and MAOB are enzymes located on the outer membranes of mitochondria, which are responsible for catalyzing monoamine oxidation. Recently, increased level of MAOs were shown in several cancer types. However, possible roles of MAOs have not yet been elucidated in the progression and prognosis of colorectal carcinoma (CRC). We therefore analyzed the importance of MAOs in CRC by an in silico analysis and tissue microarrays. Several independent cohorts indicated that high expression of MAOB, but not MAOA, was correlated with a worse disease stage and poorer survival. In total, 203 colorectal adenocarcinoma cases underwent immunohistochemical staining of MAOs, and associations with clinicopathological parameters and patient outcomes were evaluated. We found that MAOB is highly expressed in CRC tissues compared to normal colorectal tissues, and its expression was significantly correlated with a higher recurrence rate and a poor prognosis. Moreover, according to the univariate and multivariate analyses, we found that MAOB could be an independent prognostic factor for overall survival and disease-free survival, and its prognostic value was better than T and N stage. Furthermore, significant positive and negative correlations of MAOB with mesenchymal-type and epithelial-type gene expressions were observed in CRC tissues. According to the highlighted characteristics of MAOB in CRC, MAOB can be used as a novel indicator to predict the progression and prognosis of CRC patients.

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