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 HSD17B6 downregulation predicts poor prognosis and drives tumor progression via activating Akt signaling pathway in lung adenocarcinoma

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Tian Tian ◽  
Fu Hong ◽  
Zhiwen Wang ◽  
Jiaru Hu ◽  
Ni Chen ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Lung Adenocarcinoma ◽  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Grade ◽  
Tumor Stage ◽  
Advanced Tumor Stage ◽  
Large Tumor ◽  
Mesenchymal Transition ◽  
Advanced Tumor

AbstractLung adenocarcinoma is one of the most frequent tumor subtypes, involving changes in a variety of oncogenes and tumor suppressor genes. Hydroxysteroid 17-Beta Dehydrogenase 6 (HSD17B6) could synthetize dihydrotestosterone, abnormal levels of which are associated with progression of multiple tumors. Previously, we showed that HSD17B6 inhibits malignant progression of hepatocellular carcinoma. However, the mechanisms underlying inhibiting tumor development by HSD17B6 are not clear. Moreover, its role in lung adenocarcinoma (LUAD) is yet unknown. Here, we investigated its expression profile and biological functions in LUAD. Analysis of data from the LUAD datasets of TCGA, CPTAC, Oncomine, and GEO revealed that HSD17B6 mRNA and protein expression was frequently lower in LUAD than in non-neoplastic lung tissues, and its low expression correlated significantly with advanced tumor stage, large tumor size, poor tumor differentiation, high tumor grade, smoking, and poor prognosis in LUAD. In addition, its expression was negatively regulated by miR-31-5p in LUAD. HSD17B6 suppressed LUAD cell proliferation, migration, invasion, epithelial–mesenchymal transition (EMT), and radioresistance. Furthermore, HSD17B6 overexpression in LUAD cell lines enhanced PTEN expression and inhibited AKT phosphorylation, inactivating downstream oncogenes like GSK3β, β-catenin, and Cyclin-D independent of dihydrotestosterone, revealing an underlying antitumor mechanism of HSD17B6 in LUAD. Our findings indicate that HSD17B6 may function as a tumor suppressor in LUAD and could be a promising prognostic indicator for LUAD patients, especially for those receiving radiotherapy.

scholarly journals Cancer-associated fibroblast-derived SDF-1 induces epithelial-mesenchymal transition of lung adenocarcinoma via CXCR4/β-catenin/PPARδ signalling

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Yingyan Wang ◽  
Wen Lan ◽  
Mingxin Xu ◽  
Jing Song ◽  
Jun Mao ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Poor Prognosis ◽  
Molecular Mechanisms ◽  
Human Lung ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Associated Fibroblasts ◽  
Mesenchymal Transition ◽  
Cancer Associated Fibroblast ◽  
Stromal Cell Derived Factor ◽  
Targeted Approach

AbstractCancer-associated fibroblasts (CAFs) contribute to tumour epithelial-mesenchymal transition (EMT) via interaction with cancer cells. However, the molecular mechanisms underlying tumour-promoting EMT of CAFs in lung adenocarcinoma (ADC) remain unclear. Here, we observed that CAFs isolated from lung ADC promoted EMT via production of stromal cell-derived factor-1 (SDF-1) in conditioned medium (CM). CAF-derived SDF-1 enhanced invasiveness and EMT by upregulating CXCR4, β-catenin, and PPARδ, while downregulating these proteins reversed the effect. Furthermore, RNAi-mediated CXCR4 knockdown suppressed β-catenin and PPARδ expression, while β-catenin inhibition effectively downregulated PPARδ without affecting CXCR4; however, treatment with a PPARδ inhibitor did not inhibit CXCR4 or β-catenin expression. Additionally, pairwise analysis revealed that high expression of CXCR4, β-catenin, and PPARδ correlated positively with 75 human lung adenocarcinoma tissues, which was predictive of poor prognosis. Thus, targeting the CAF-derived, SDF-1-mediated CXCR4 β-catenin/ PPARδ cascade may serve as an effective targeted approach for lung cancer treatment.

scholarly journals SOX5 predicts poor prognosis in lung adenocarcinoma and promotes tumor metastasis through epithelial-mesenchymal transition

Oncotarget ◽  
2017 ◽  
Vol 9 (13) ◽  
pp. 10891-10904 ◽  
Author(s):  
Xin Chen ◽  
Yufei Fu ◽  
Hongfei Xu ◽  
Peng Teng ◽  
Qiong Xie ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Poor Prognosis ◽  
Tumor Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition

scholarly journals High Expression of BCAR1 by Circulating Tumor Cells and Tumor Tissues Is Predictive of a Poor Prognosis of Early-Stage Lung Adenocarcinoma Potentially Due to Regulation of Epithelial-Mesenchymal Transition

2020 ◽  
Vol 19 ◽  
pp. 153303382098308
Author(s):  
Shasha Jiang ◽  
Chunguo Mao ◽  
Bin Jiang ◽  
Qunyou Tan ◽  
Bo Deng
Keyword(s):  
Lung Adenocarcinoma ◽  
Tumor Cells ◽  
Clinical Significance ◽  
Peripheral Blood ◽  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Early Stage ◽  
Healthy Controls ◽  
Mesenchymal Transition ◽  
Tumor Tissues

Objective: To clarify the clinical significance of breast cancer anti-estrogen resistance protein 1 (BCAR1) expression in circulating tumor cells (CTCs) in the peripheral blood and tumor tissues in patients with early stage lung adenocarcinoma (ES-LUAD). Methods: The study cohort included 60 patients with stage I LUAD (50 IA and 10 IB) who underwent surgery from November 2015 to November 2018 and 31 healthy controls. The expression levels of BCAR1 and markers of epithelial-mesenchymal transition (EMT) in peripheral blood CTCs were detected using CanPatrolTM technology before surgery, and immunohistochemical analysis was used to detect BCAR1 expression in tumor tissues collected from 40 patients. The predictive power of BCAR1 expression in CTCs and tumor tissues on disease-free survival (DFS) was analyzed. The Cancer Genome Atlas (TCGA) database was used to study BCAR1 expression and overall survival as validation. The Gene Expression Profiling Interactive Analysis online tool was used to analyze the correlations between the expression levels of BCAR1 and EMT molecular markers. Results: Both the number and detection rates of BCAR1-negative CTCs and BCAR1-positive CTCs in peripheral blood of lung cancer patients were significantly higher as compared with healthy controls ( p < 0.05). BCAR1-positive CTCs more commonly co-expressed both epithelial and mesenchymal markers. Kaplan–Meier analysis demonstrated that patients with BCAR1(++) CTCs in peripheral blood before surgery were more prone to recurrence or metastasis after 2 years. COX analysis showed that patients with higher abundance of BCAR1(++) CTCs had a poorer prognosis (hazard ratio [HR] = 1.712, 95% confidence interval [CI] = 1.077–2.272, p = 0.023). Furthermore, high BCAR1 expression in tumor tissues was predictive of a poor prognosis (HR = 2.654, 95% CI = 1.239–5.686, p = 0.012), as validated by TCGA database (HR = 2.217, 95% CI = 1.069–4.595, p = 0.032). In addition, BCAR1 expression in LUAD tissues from TCGA was significantly positively correlated with the expression of both epithelial markers (e.g., ck8/18/19) and mesenchymal markers (e.g., vimentin and twist). Conclusion: BCAR1 may have a “dual impact” on EMT markers in tumor tissues and CTCs due to micro-environmental disparities, resulting in important clinical significance, which can potentially guide accurate treatment of LUAD.

scholarly journals Upregulation of LINC01426 promotes the progression and stemness in lung adenocarcinoma by enhancing the level of SHH protein to activate the hedgehog pathway

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Xiaoli Liu ◽  
Zuwei Yin ◽  
Linping Xu ◽  
Huaimin Liu ◽  
Lifeng Jiang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Bioinformatics Analysis ◽  
Epithelial Mesenchymal Transition ◽  
Mrna Level ◽  
Hedgehog Pathway ◽  
Biological Processes ◽  
Protein Coding ◽  
Mesenchymal Transition ◽  
Functional Roles ◽  
Rip Assay

AbstractLong noncoding RNAs (lncRNAs) play crucial roles in regulating a variety of biological processes in lung adenocarcinoma (LUAD). In our study, we mainly explored the functional roles of a novel lncRNA long intergenic non-protein coding RNA 1426 (LINC01426) in LUAD. We applied bioinformatics analysis to find the expression of LINC01426 was upregulated in LUAD tissue. Functionally, silencing of LINC01426 obviously suppressed the proliferation, migration, epithelial–mesenchymal transition (EMT), and stemness of LUAD cells. Then, we observed that LINC01426 functioned through the hedgehog pathway in LUAD. The effect of LINC01426 knockdown could be fully reversed by adding hedgehog pathway activator SAG. In addition, we proved that LINC01426 could not affect SHH transcription and its mRNA level. Pull-down sliver staining and RIP assay revealed that LINC01426 could interact with USP22. Ubiquitination assays manifested that LINC01426 and USP22 modulated SHH ubiquitination levels. Rescue assays verified that SHH overexpression rescued the cell growth, migration, and stemness suppressed by LINC01426 silencing. In conclusion, LINC01426 promotes LUAD progression by recruiting USP22 to stabilize SHH protein and thus activate the hedgehog pathway.

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