scholarly journals Analysis of the role of METTL5 as a hub gene in lung adenocarcinoma based on a weighted gene co-expression network

2021 ◽  
Vol 18 (5) ◽  
pp. 6608-6619
Author(s):  
Xinwang Yan ◽  
◽  
Xiaowen Zhao ◽  
Qing Yan ◽  
Ye Wang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Differential Expression ◽  
Epithelial Mesenchymal Transition ◽  
Differential Expression Analysis ◽  
Predictive Performance ◽  
Tumor Stage ◽  
Malignant Progression ◽  
Mesenchymal Transition ◽  
Kaplan Meier ◽  
Differential Expression Genes

<abstract> <p>Lung adenocarcinoma (LUAD) is a frequently diagnosed malignant tumor that is highly invasive and lethal. The prognosis of patients with LUAD still needs to be improved, as conventional treatment is remarkably well tolerated. In this study, the expression profile of LUAD in the TCGA database was used for differential expression analysis, and differential expression genes were determined to construct a weighted gene co-expression network analysis (WGCNA) for dividing and finding the gene modules with the highest correlation with tumor stage. Here, METTL5, DDX23, GPSM2, CEP95, WDCP, and METL17 were identified as hub genes. According to the relation degree, METTL5 was determined as the candidate gene in this study. Difference analysis and receiver operating characteristic (ROC) curve were applied to identify the predictive performance of METTL5 in LUAD, and Kaplan-Meier (KM) analysis showed that the prognosis of LUAD patients with high METTL5 expression was poor. Further GSEA analysis showed that high-expressed METTL5 was related to epithelial-mesenchymal transition and other pathways. Therefore, METTL5 may be involved in the occurrence and malignant progression of LUAD. The current findings provide an effective molecular target for early diagnosis of LUAD, helping monitor the malignant progression of LUAD and improve the prognosis of LUAD patients.</p> </abstract>

scholarly journals Co-Expression of Coxsackievirus/Adenovirus Receptors and Desmoglein 2 in Lung Adenocarcinoma: A Comprehensive Analysis of Bioinformatics and Tissue Microarrays

2020 ◽  
Vol 9 (11) ◽  
pp. 3693
Author(s):  
Ching-Fu Weng ◽  
Chi-Jung Huang ◽  
Mei-Hsuan Wu ◽  
Henry Hsin-Chung Lee ◽  
Thai-Yen Ling
Keyword(s):  
Overall Survival ◽  
Survival Analysis ◽  
Lung Adenocarcinoma ◽  
Cox Regression ◽  
Epithelial Mesenchymal Transition ◽  
Early Stage ◽  
The Cancer Genome Atlas ◽  
Cancer Tissue ◽  
Mesenchymal Transition ◽  
Kaplan Meier

Introduction: Coxsackievirus/adenovirus receptors (CARs) and desmoglein-2 (DSG2) are similar molecules to adenovirus-based vectors in the cell membrane. They have been found to be associated with lung epithelial cell tumorigenesis and can be useful markers in predicting survival outcome in lung adenocarcinoma (LUAD). Methods: A gene ontology enrichment analysis disclosed that DSG2 was highly correlated with CAR. Survival analysis was then performed on 262 samples from the Cancer Genome Atlas, forming “Stage 1A” or “Stage 1B”. We therefore analyzed a tissue microarray (TMA) comprised of 108 lung samples and an immunohistochemical assay. Computer counting software was used to calculate the H-score of the immune intensity. Cox regression and Kaplan–Meier analyses were used to determine the prognostic value. Results: CAR and DSG2 genes are highly co-expressed in early stage LUAD and associated with significantly poorer survival (p = 0.0046). TMA also showed that CAR/DSG2 expressions were altered in lung cancer tissue. CAR in the TMA was correlated with proliferation, apoptosis, and epithelial–mesenchymal transition (EMT), while DSG2 was associated with proliferation only. The Kaplan–Meier survival analysis revealed that CAR, DSG2, or a co-expression of CAR/DSG2 was associated with poorer overall survival. Conclusions: The co-expression of CAR/DSG2 predicted a worse overall survival in LUAD. CAR combined with DSG2 expression can predict prognosis.

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 SPAG5 Expression Correlated With Prognostic Implication and Immune Infiltration in Lung Adenocarcinoma

2022 ◽  
Author(s):  
Jianjiang Xie ◽  
Xie Xu ◽  
Huaping Zhou
Keyword(s):  
Lung Adenocarcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Underlying Mechanism ◽  
Immune Checkpoints ◽  
Dna Damage And Repair ◽  
Mesenchymal Transition ◽  
Immune Infiltration ◽  
Kaplan Meier ◽  
Associate Antigen ◽  
Cd4 Cell

Abstract Background Sperm-associate antigen 5 (SPAG5) is a critical oncogene in several cancers. But the role of SPAG5A in lung adenocarcinoma (LUAD) remains unclear. Thus, the aims of our study are to explore the function and underlying mechanism of SPAG5 in LUAD. Methods Expression of SPAG5 was determined using the Oncomine, TIMER, and GEPIA databases. Correlation of SPAG5 and survival was detected by GEPIA database, PrognoScan, Kaplan-Meier Plotter databases. And the association between SPAG5 and tumor malignant phenotypes were analyzed by the CancerSEA. Besides, the correlation between SPAG5 expression and tumor immune infiltration as well as immune checkpoints were analyzed by TIMER. the co-expression genes of SPAG5 were identified using STRING, and the mutation and biological function of SPAG5 and its co-expression genes were determined by cBioPortal and Metascape, respectively. Finally, the SPAG5 expression in LUAD samples was determined by tissues microarrays (TMA) and immunohistochemistry (IHC) analyses.Results We found that upregulated SPAG5 associated with poor survival of LUAD patients. Besides, SPAG5 expression associated to B cell, CD4+ cell, CD8+ cell, macrophage, DC cell as well as CD274, CTLA4, GZMB, LAG3, PDCD1, TIGIT in LUAD. SPAG5 expression also associated with cell proliferation, cell cycle, DNA damage and repair, epithelial-mesenchymal transition (EMT), invasion, and stemness, inflammation in LUAD. Conclusion Our finding indicated that SPAG5 acted as a crucial oncogene in LUAD, and correlated with unfavorable survival as well as tumor infiltration inflation.

scholarly journals Individualized lncRNA differential expression profile reveals heterogeneity of breast cancer

Oncogene ◽  
2021 ◽  
Author(s):  
Zhangxiang Zhao ◽  
YingYing Guo ◽  
Yaoyao Liu ◽  
Lichun Sun ◽  
Bo Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Differential Expression ◽  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Breast Cancer Subtype ◽  
Differential Expression Analysis ◽  
Differentially Expressed ◽  
Migration And Invasion ◽  
Response Analysis ◽  
Mesenchymal Transition

AbstractLong non-coding RNAs (lncRNAs) play key regulatory roles in breast cancer. However, population-level differential expression analysis methods disregard the heterogeneous expression of lncRNAs in individual patients. Therefore, we individualized lncRNA expression profiles for breast invasive carcinoma (BRCA) using the method of LncRNA Individualization (LncRIndiv). After evaluating the robustness of LncRIndiv, we constructed an individualized differentially expressed lncRNA (IDElncRNA) profile for BRCA and investigated the subtype-specific IDElncRNAs. The breast cancer subtype-specific IDElncRNA showed frequent co-occurrence with alterations of protein-coding genes, including mutations, copy number variation and differential methylation. We performed hierarchical clustering to subdivide TNBC and revealed mesenchymal subtype and immune subtype for TNBC. The TNBC immune subtype showed a better prognosis than the TNBC mesenchymal subtype. LncRNA PTOV1-AS1 was the top differentially expressed lncRNA in the mesenchymal subtype. And biological experiments validated that the upregulation of PTOV1-AS1 could downregulate TJP1 (ZO-1) and E-Cadherin, and upregulate Vimentin, which suggests PTOV1-AS1 may promote epithelial-mesenchymal transition and lead to migration and invasion of TNBC cells. The mesenchymal subtype showed a higher fraction of M2 macrophages, whereas the immune subtype was more associated with CD4 + T cells. The immune subtype is characterized by genomic instability and upregulation of immune checkpoint genes, thereby suggesting a potential response to immunosuppressive drugs. Last, drug response analysis revealed lncRNA ENSG00000230082 (PRRT3-AS1) is a potential resistance biomarker for paclitaxel in BRCA treatment. Our analysis highlights that IDElncRNAs can characterize inter-tumor heterogeneity in BRCA and the new TNBC subtypes indicate novel insights into TNBC immunotherapy.

scholarly journals Identification of Epithelial-Mesenchymal Transition-Related lncRNAs that Associated With the Prognosis and Immune Microenvironment in Colorectal Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Chuan Liu ◽  
Chuan Hu ◽  
Jianyi Li ◽  
Liqing Jiang ◽  
Chengliang Zhao
Keyword(s):  
Colorectal Cancer ◽  
Functional Analysis ◽  
Cox Regression ◽  
Epithelial Mesenchymal Transition ◽  
Risk Group ◽  
Differential Expression Analysis ◽  
Disease Free Survival ◽  
Immune Microenvironment ◽  
Mesenchymal Transition ◽  
Kaplan Meier

Background: The expression of long non-coding RNA (lncRNA) is associated with the epithelial-mesenchymal transition (EMT) in tumorigenicity, but the role of EMT-related lncRNA in colorectal cancer (CRC) remains unclear.Methods: The clinical data and gene expression profile of CRC patients were obtained from The Cancer Genome Atlas database. Differential expression analysis, Cox regression model, and Kaplan-Meier analysis were used to study the relationship between EMT-related lncRNAs and the prognosis of CRC. Functional analysis and unsupervised clustering analysis were performed to explore the influence of certain lncRNAs on CRC. Finally, Cytoscape was used to construct mRNA-lncRNA networks.Results: Two signatures incorporating six and ten EMT-related lncRNAs were constructed for predicting the overall survival (OS) and disease-free survival (DFS), respectively. Kaplan-Meier survival curves indicated that patients in the high-risk group had a poorer prognosis than those in the low-risk group. The results of the functional analysis suggested that the P53 and ECM-receptor pathways affect the prognosis of CRC, and AL591178.1 is a key prognostic EMT-related lncRNA, which is negatively related to immune cells, P53 pathway, and ECM-receptor pathway.Conclusion: Six OS-related and ten DFS-related EMT-related lncRNAs were correlated with the prognosis of CRC by potentially affecting the immune microenvironment, and AL591178.1 plays a key role as a prognostic factor.

scholarly journals CNTN-1 Enhances Chemoresistance in Human Lung Adenocarcinoma Through Induction of Epithelial-Mesenchymal Transition by Targeting the PI3K/Akt Pathway

2017 ◽  
Vol 43 (2) ◽  
pp. 465-480 ◽  
Author(s):  
Ruijie Zhang ◽  
Shenghua Sun ◽  
Fuyun Ji ◽  
Chun Liu ◽  
Hua Lin ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cisplatin Resistance ◽  
Epithelial Mesenchymal Transition ◽  
A549 Cells ◽  
Malignant Progression ◽  
Akt Pathway ◽  
Vimentin Expression ◽  
Mesenchymal Transition

Background/Aims: Chemoresistance has been a major obstacle to the effective treatment of lung cancer. Previously, we found that contactin-1 (CNTN-1) is related to cisplatin resistance in lung adenocarcinoma. Here, we aimed to investigate the underlying mechanism behind the role of CNTN-1 in cisplatin resistance in lung adenocarcinoma. Methods: EMT-associated phenotypes, including alterations in cellular morphology and marker (E-cadherin, N-cadherin and Vimentin) expression, were compared between A549 cells and A549/DDP cells (a cisplatin-resistant cell line of lung adenocarcinoma with abnormal CNTN-1 expression) by using real-time time PCR and Western blotting. Other methods, including CNTN-1 overexpression in A549 cells and CNTN-1 knockdown in A549/DDP cells, were also used to investigate the role of CNTN-1 in mediating the EMT phenotype and thr resulting cisplatin resistance and malignant progression of cancer cells in vitro and in vivo. Results: A549/DDP cells exhibited an EMT phenotype and aggravated malignant behaviors. CNTN-1 knockdown in A549/DDP cells partly reversed the EMT phenotype, increased drug sensitivity, and attenuated the malignant progression whereas CNTN-1 overexpression in A549 cells resulted in the opposite trend. Furthermore, the PI3K/Akt pathway was involved in the effects of CNTN-1 on EMT progression in A549/DDP cells, verified by the xenograft mouse model. Conclusion: CNTN-1 promotes cisplatin resistance in human cisplatin-resistant lung adenocarcinoma through inducing the EMT process by activating the PI3K/Akt signaling pathway. CNTN-1 may be a potential therapeutic target to reverse chemoresistance in cisplatin-resistant lung adenocarcinoma.

scholarly journals Overexpressed P75CUX1 promotes EMT in glioma infiltration by activating β-catenin

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Anqi Xu ◽  
Xizhao Wang ◽  
Jie Luo ◽  
Mingfeng Zhou ◽  
Renhui Yi ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Tumor Grade ◽  
Prognostic Indicator ◽  
Migration And Invasion ◽  
Poor Overall Survival ◽  
Mesenchymal Transition ◽  
Kaplan Meier ◽  
Homeobox Protein

AbstractThe homeobox protein cut-like 1 (CUX1) comprises three isoforms and has been shown to be involved in the development of various types of malignancies. However, the expression and role of the CUX1 isoforms in glioma remain unclear. Herein, we first identified that P75CUX1 isoform exhibited consistent expression among three isoforms in glioma with specifically designed antibodies to identify all CUX1 isoforms. Moreover, a significantly higher expression of P75CUX1 was found in glioma compared with non-tumor brain (NB) tissues, analyzed with western blot and immunohistochemistry, and the expression level of P75CUX1 was positively associated with tumor grade. In addition, Kaplan–Meier survival analysis indicated that P75CUX1 could serve as an independent prognostic indicator to identify glioma patients with poor overall survival. Furthermore, CUX1 knockdown suppressed migration and invasion of glioma cells both in vitro and in vivo. Mechanistically, this study found that P75CUX1 regulated epithelial–mesenchymal transition (EMT) process mediated via β-catenin, and CUX1/β-catenin/EMT is a novel signaling cascade mediating the infiltration of glioma. Besides, CUX1 was verified to promote the progression of glioma via multiple other signaling pathways, such as Hippo and PI3K/AKT. In conclusion, we suggested that P75CUX1 could serve as a potential prognostic indicator as well as a novel treatment target in malignant glioma.

scholarly journals A novel homeostatic loop of sorcin drives paclitaxel-resistance and malignant progression via Smad4/ZEB1/miR-142-5p in human ovarian cancer

Oncogene ◽  
2021 ◽  
Author(s):  
Jinguo Zhang ◽  
Wencai Guan ◽  
Xiaolin Xu ◽  
Fanchen Wang ◽  
Xin Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Calcium Binding ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Progression ◽  
Bioinformatics Analyses ◽  
Aberrant Expression ◽  
Mesenchymal Transition ◽  
E Box

AbstractThe primary chemotherapy of ovarian cancer (OC) often acquires chemoresistance. Sorcin (SRI), a soluble resistance-related calcium-binding protein, has been reported to be an oncogenic protein in cancer. However, the molecular mechanisms of SRI regulation and the role and aberrant expression of SRI in chemoresistant OC remain unclear. Here, we identified SRI as a key driver of paclitaxel (PTX)-resistance and explored its regulatory mechanism. Using transcriptome profiles, qRT-PCR, proteomics, Western blot, immunohistochemistry, and bioinformatics analyses, we found that SRI was overexpressed in PTX-resistant OC cells and the overexpression of SRI was related to the poor prognosis of patients. SRI was a key molecule required for growth, migration, and PTX-resistance in vitro and in vivo and was involved in epithelial–mesenchymal transition (EMT) and stemness. Mechanistic studies showed that miR-142-5p directly bound to the 3ʹ-UTR of SRI to suppress its expression, whereas a transcription factor zinc-finger E-box binding homeobox 1 (ZEB1) inhibited the transcription of miR-142-5p by directly binding to the E-box fragment in the miR-142 promoter region. Furthermore, ZEB1 was negatively regulated by SRI which physically interacted with Smad4 to block its translocation from the cytosol to the nucleus. Taken together, our findings unveil a novel homeostatic loop of SRI that drives the PTX-resistance and malignant progression via Smad4/ZEB1/miR-142-5p in human OC. Targeting this SRI/Smad4/ZEB1/miR-142-5p loop may reverse the PTX-resistance.

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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