scholarly journals Aberrant upregulation of TNFRSF21 enhances tumor aggressiveness in lung cancer via activation of the ERK/FOXM1 signaling cascade

2021 ◽  
Author(s):  
Chengwei Zhou ◽  
Zixuan Chen ◽  
Jiayan Liu ◽  
Shuai Fang
Keyword(s):  
Lung Cancer ◽  
Immunohistochemical Analysis ◽  
Gene Expression Omnibus ◽  
Nsclc Cell ◽  
Tissue Array ◽  
Cancer Tissue ◽  
Tumor Aggressiveness ◽  
Lung Cancers ◽  
Ncbi Gene Expression Omnibus ◽  
Downstream Target

Abstract Background Lung cancer is one of the leading causes of cancer-related death worldwide. Identifying alterations in oncogenic drivers are known to be an effective strategy to explore potential druggable targets in the treatment of this disease. Methods Integrative analysis of the NCBI Gene Expression Omnibus (GEO) datasets by R language identified TNFRSF21 is upregulated in lung cancers. Using overexpression or knockdown approach to demonstrate the gene effect and mechanisms on lung cancer cells. Immunohistochemical analysis of a commercial lung cancer tissue array showed clinic-pathological correlations. Results TNFRSF21 is frequently upregulated and associated with high-grade tumors and is highly correlated with advanced NSCLC. Biochemical studies confirmed that TNFRSF21 overexpression could markedly promote NSCLC cell growth and cell migration/invasion, while suppression of ERK and FOXM1 by U0126 and thiostrepton, respectively, could significantly counteract TNFRSF21-mediated NSCLC cell proliferation and aggressiveness. Mechanistic studies revealed that forced expression or ablation of TNFRSF21 could escalate or attenuate both the phosphorylation of ERK (p-ERK) and the expression of FOXM1, respectively, whereas the levels of TNFRSF21 and p-ERK were not altered when FOXM1 was inhibited by thiostrepton. On the contrary, inhibition of the intensity of p-ERK by U0126 could reduce FOXM1 expression in TNFRSF21-overexpressing NSCLC cells, which suggests that TNFRSF21 is the upstream effector of ERK signaling and that its downstream target is FOXM1. Conclusions This study highlights the significance of TNFRSF21 in promoting tumor aggressiveness in lung cancer by increasing ERK/FOXM1 signaling, which suggests that targeting TNFRSF21/MEK/ERK/FOXM1 may represent a potential therapy for lung cancer.

scholarly journals Prognostic values, ceRNA network, and immune regulation function of SDPR in KRAS-mutant lung cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaoqing Luo ◽  
Shunli Peng ◽  
Sijie Ding ◽  
Qin Zeng ◽  
Rong Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint ◽  
Cox Regression ◽  
Tissue Array ◽  
Lung Cancers ◽  
Cox Regression Analysis ◽  
Immune Checkpoint Molecules ◽  
Cerna Network ◽  
Kaplan Meier ◽  
Infiltration Models

Abstract Background Serum Deprivation Protein Response (SDPR) plays an important role in formation of pulmonary alveoli. However, the functions and values of SDPR in lung cancer remain unknown. We explored prognostic value, expression pattern, and biological function of SDPR in non-small cell lung cancer (NSCLC) and KRAS-mutant lung cancers. Methods SDPR expression was evaluated by quantitative real-time PCR (RT-qPCR), immunohistochemistry (IHC), and Western blot on human NSCLC cells, lung adenocarcinoma tissue array, KRAS-mutant transgenic mice, TCGA and GEO datasets. Prognostic values of SDPR were evaluated by Kaplan–Meier and Cox regression analysis. Bioinformatics implications of SDPR including SDPR-combined transcription factors (TFs) and microRNAs were predicted. In addition, correlations between SDPR, immune checkpoint molecules, and tumor infiltration models were illustrated. Results SDPR expression was downregulated in tumor cells and tissues. Low SDPR expression was an independent factor that correlated with shorter overall survival of patients both in lung cancer and KRAS-mutant subgroups. Meanwhile, ceRNA network was constructed to clarify the regulatory and biological functions of SDPR. Negative correlations were found between SDPR and immune checkpoint molecules (PD-L1, TNFRSF18, TNFRSF9, and TDO2). Moreover, diversity immune infiltration models were observed in NSCLC with different SDPR expression and copy number variation (CNV) patterns. Conclusions This study elucidated regulation network of SDPR in KRAS-mutant NSCLC, and it illustrated correlations between low SDPR expression and suppressed immune system, unfolding a prognostic factor and potential target for the treatment of lung cancer, especially for KRAS-mutant NSCLC.

Expression of CD133, a possible marker for cancer stem cells (CSCs), in small cell lung cancer (SCLC) cell lines and non- small cell lung cancer (NSCLC) cell lines

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22100-e22100
Author(s):  
T. Hayashi ◽  
H. Tao ◽  
M. Jida ◽  
T. Kubo ◽  
H. Yamamoto ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nsclc Cell ◽  
Small Cell Lung ◽  
Lung Cancers

e22100 Background: Cancer stem cell (CSCs) are believed to play important roles in tumor development, recurrence or metastasis. Identification of CSCs may have a therapeutic significance. CD133 expression has been shown on a minority of various human cancer cells with high capability of self-renewal and proliferation. Therefore, CD133 is thought to be one of possible markers for CSCs. Regarding human lung cancers, the existence, prevalence or roles of CD133 positive cells has not been fully understood. Methods: We examined CD133 mRNA by quantitative real-time PCR and sorted CD133-positive cells by fluorescence-activated cell sorting (FACS) using human small cell lung cancer(SCLC) and non-small cell lung cancer (NSCLC) cell lines. We evaluated differences of cell proliferation between CD133-positive and -negative cells by MTS assay in vitro and by subcutaneous injection for non- obese diabetic/severe combined immunodeficiency (NOD/SCID) mice in vivo. Results: CD133 expression was almost restricted in SCLC cell lines. CD133 mRNA expression or CD133-positive cell population was scarcely observed in NSCLC cell lines. In two SCLC cell lines examined (NCI-H82 and NCI-H69), CD133 positive cells had higher tumorgenicity both in vivo and in vitro than NSCLC cell lines. Conclusions: The expression status of CD133 is totally different between NSCLCs and SCLCs, probably reflecting the difference of these progenitor cells. Our results indicate that CD133-positive cells in SCLC cell are responsible for tumor growth. However, in view of their wide prevalence, CD133-positive cells do not seem to be a candidate for CSCs, at least in cell lines. To investigate the molecular and functional characteristics of CD133-positive cells may lead to a new therapeutic strategy for human lung cancers, especially for SCLCs. No significant financial relationships to disclose.

Screening of NSCLC samples from Chinese lung cancer patients for activating rearrangements of the ALK, RET, and ROS1 genes.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22066-e22066
Author(s):  
Li-Mou Zheng ◽  
David B. Whyte ◽  
Li Ruan ◽  
Roman Song ◽  
Luo Fei ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Real Time ◽  
Real Time Pcr ◽  
Kinase Inhibitors ◽  
Ffpe Tissue ◽  
Cancer Tissue ◽  
Fusion Genes ◽  
Tissue Samples ◽  
Lung Cancers ◽  
Pcr Assays

e22066 Background: The ALK, RET, and ROS1 genes are involved in gene rearrangements in a fraction of non-small cell lung cancers. The resulting oncogenic fusion genes define molecular sub-types of NSCLC with distinct sensitivities to treatment with various kinase inhibitors. We developed real-time reverse transcriptase PCR assays to detect rearrangements of ALK, RET, and ROS1 in FFPE lung cancer tissue. Methods: mRNA from NSCLC FFPE tissue samples was reverse transcribed to cDNA. Multiplex quantitative PCR was performed to detect 9 variants of EML4-ALK fusions, 9 variants of RET fusions and 14 variants of ROS1 fusions. A total of 409 samples were analyzed: 267 were classified as adenocarcinoma, 104 as squamous cell carcinoma and 38 had undetermined histology. EGFR and KRAS mutation status is unknown. The junctions of fusion-positive samples were sequenced by Sanger sequencing. Results: Among the 409 NSCLC specimens tested the frequency was 5.4% (22/409) for EML4-ALK fusions, 1.5% (6/409) for RET fusions, and 2.2% (9/409) for ROS1 fusions. EML4-ALK fusions were more prevalent in patients that were less than 60 years old (9.1% versus 2.0%, p= 0.004). The TNM stage was not correlated with the presence of any of the fusions. The table below lists the frequencies for specific rearrangements as determined by sequencing the real-time PCR products. Conclusions: Real-time PCR assays based on cDNA from FFPE tissue can identify patients with ALK, RET and ROS1 fusion genes. The ALK, RET and ROS1 assays will allow selection of patients most likely to respond to therapies that specifically target these cancer drivers. Further clinical testing of NSCLC patients in the Chinese population will be performed to support SFDA registration of these assays in China. [Table: see text]

scholarly journals Prognostic values, ceRNA network, and immune regulation function of SDPR in KRAS-mutant lung cancer

2021 ◽  
Author(s):  
Xiaoqing Luo ◽  
Shunli Peng ◽  
Sijie Ding ◽  
Qin Zeng ◽  
Rong Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint ◽  
Cox Regression ◽  
Tissue Array ◽  
Lung Cancers ◽  
Cox Regression Analysis ◽  
Immune Checkpoint Molecules ◽  
Cerna Network ◽  
Kaplan Meier ◽  
Infiltration Models

Abstract Background: Serum Deprivation Protein Response (SDPR) plays an important role in formation of pulmonary alveoli. However, the functions and values of SDPR in lung cancer remain unknown. We explored prognostic value, expression pattern, and biological function of SDPR in non-small cell lung cancer (NSCLC) and KRAS-mutant lung cancers.Methods: SDPR expression was evaluated by quantitative real-time PCR (RT-qPCR), immunohistochemistry (IHC), and Western blot on human NSCLC cells, lung adenocarcinoma tissue array, KRAS-mutant transgenic mice, TCGA and GEO datasets. Prognostic values of SDPR were evaluated by Kaplan–Meier and Cox regression analysis. Bioinformatics implications of SDPR including SDPR-combined transcription factors (TFs) and microRNAs were predicted. In addition, correlations between SDPR, immune checkpoint molecules, and tumor infiltration models were illustrated.Results: SDPR expression was downregulated in tumor cells and tissues. Low SDPR expression was an independent factor that correlated with shorter overall survival of patients both in lung cancer and KRAS-mutant subgroups. Meanwhile, ceRNA network was constructed to clarify the regulatory and biological functions of SDPR. Negative correlations were found between SDPR and immune checkpoint molecules (PD-L1, TNFRSF18, TNFRSF9, and TDO2). Moreover, diversity immune infiltration models were observed in NSCLC with different SDPR expression and copy number variation (CNV) patterns.Conclusions: This study elucidated regulation network of SDPR in KRAS-mutant NSCLC, and it illustrated correlations between low SDPR expression and suppressed immune system, unfolding a prognostic factor and potential target for the treatment of lung cancer, especially for KRAS-mutant NSCLC.

scholarly journals IL-13 Augments Histone Demethylase JMJD2B/KDM4B Expression Levels, Activity, and Nuclear Translocation in Airway Fibroblasts in Asthma

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Khuloud Bajbouj ◽  
Mahmood Y. Hachim ◽  
Rakhee K. Ramakrishnan ◽  
Huwaida Fazel ◽  
Jumana Mustafa ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Immunohistochemical Analysis ◽  
Bioinformatic Analysis ◽  
Gene Expression Omnibus ◽  
Histone Demethylase ◽  
Lung Fibroblasts ◽  
Expression Levels ◽  
Downstream Target ◽  
Gene And Protein Expression ◽  
Bronchial Biopsies

Purpose. Asthma is one of the most common obstructive pulmonary diseases worldwide. Epigenetic alterations, including DNA methylation and histone modifications, have been reported to contribute to asthma pathogenesis. Since the inflammation mediator and remodeling trigger, IL-13, is known to play a central role in the pathophysiology of asthma, this study was aimed to identify novel IL-13-regulated epigenetic modifiers in asthma that may contribute to subepithelial fibrosis. Methods. Publicly available transcriptomic datasets from Gene Expression Omnibus (GEO) were used to identify differentially expressed genes on an epigenetic level upon IL-13 exposure in lung fibroblasts. Bronchial fibroblasts isolated from healthy and asthmatic individuals were assessed for the gene and protein expression levels of the identified gene at baseline and upon IL-13 treatment using qRT-PCR and western blotting, respectively. Its subcellular localization and tissue distribution were examined in bronchial fibroblasts as well as bronchial biopsies by immunofluorescence and immunohistochemical analysis, respectively. Results. Bioinformatic analysis revealed the differential expression of the histone demethylase JMJD2B/KDM4B, a well-known epigenetic modulator that leads to the demethylation of different lysine residues on histones, in IL-13-treated lung fibroblasts. The baseline expression levels of JMJD2B were higher in asthmatic fibroblasts and in bronchial biopsies in comparison to healthy ones. There was also an increase in JMJD2B activity as evidenced by the demethylation of its downstream target, H3K36me3. Furthermore, IL-13 stimulation induced JMJD2B expression and further demethylation of H3K36me3 in asthmatic fibroblasts. This was accompanied by increased translocation of JMJD2B into the nucleus. Conclusion. This study highlights the novel pathological involvement of the histone demethylase JMJD2B/KDM4B in asthmatic airway fibroblasts that are regulated by IL-13. Clinical implications. Given that there is no single therapeutic medicine to effectively treat the various subtypes of asthma, this study provides promising insights into JMJD2B as a new therapeutic target that could potentially improve the treatment and management of asthma.

Quescin Sulfhydryl Oxidase 1 (QSOX1) Secreted by Lung Cancer cells Promotes Cancer Metastasis

2018 ◽  
Author(s):  
Hye-Jin Sung ◽  
Jung-Mo Ahn ◽  
Yeon-Hee Yoon ◽  
Sang-su Na ◽  
Young-Jin Choi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Cancer Tissue ◽  
Sulfhydryl Oxidase ◽  
Lung Cancers ◽  
Normal Tissues ◽  
Cancer Tissues

As lung cancer shows the highest mortality in cancer related death, serum biomarkers are demanded for the lung cancer diagnosis and its treatment. To discover lung cancer protein biomarkers, secreted proteins from primary cultured lung cancer and adjacent normal tissues from patients were subjected to LC/MS-MS proteomic analysis. Quescin sulfhydryl oxidase (QSOX1) was selected as a biomarker candidate from the proteins enriched in the secretion of lung cancer cells. QSOX1 levels were higher in 82% (51 of 62 tissues) of lung cancer tissues compared to adjacent normal tissues. Importantly, QSOX1 serum levels were significantly higher in cancer patients (p<0.05, AUC=0.89), when measured by multiple reaction monitoring (MRM). Higher levels of QSOX1 are also uniquely detected in lung cancer tissues among several other solid cancers by immunohistochemistry. QSOX1 knock-downed Lewis lung cancer (LLC) cells was less viable from oxidative stress and had reduced migration and invasion. In addition, LLC mouse models with QSOX1 knock-down also proved that QSOX1 functions in promoting cancer metastasis. In conclusion, QSOX1 might be a lung cancer tissue-derived biomarker and involved in the promotion of lung cancers, and thus can be a therapeutic target for lung cancers.

scholarly journals Circular RNA circ_103820 suppresses lung cancer tumorigenesis by sponging miR-200b-3p to release LATS2 and SOCS6

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Yongbin Chi ◽  
Wenlong Zheng ◽  
Guangyu Bao ◽  
Lifeng Wu ◽  
Xiaoxue He ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Target Genes ◽  
Circular Rna ◽  
Gene Expression Omnibus ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Inhibitory Effects ◽  
Downstream Target ◽  
Direct Target ◽  
Tumor Suppressive Function

AbstractA growing number of circular RNAs (circRNAs) have been identified and verified in several cancers. However, highly efficient therapeutic methods based on circRNAs in lung cancer remain largely unexplored. In the present study, we identified a novel circular RNA, hsa_circ_103820, based on Gene Expression Omnibus (GEO) data. Functionally, overexpression of hsa_circ_103820 showed significant inhibitory effects on the proliferation, migration and invasion of lung cancer cells, and knockdown of hsa_circ_103820 played promoting roles. Regarding the mechanism, we revealed that miR-200b-3p was a direct target of hsa_circ_103820 and that LATS2 and SOCS6 were the downstream target genes of miR-200b-3p. Therefore, we identified a novel potential tumor suppressive function of hsa_circ_103820 in lung cancer.

scholarly journals Analysis the susceptibility of lung cancer patients to SARS-CoV-2 infection

2020 ◽  
Author(s):  
Qi Kong
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Meta Analysis ◽  
Lung Squamous Cell Carcinoma ◽  
Gene Expression Omnibus ◽  
Lung Cancers ◽  
Lung Cancer Patients ◽  
Angiotensin I Converting Enzyme ◽  
Novel Coronavirus ◽  
Transmembrane Serine Protease

Abstract Recent studies have reported that 2019 novel coronavirus disease (COVID-19) patients with lung cancer have a higher risk of severe events than patients without cancer. In this study, we investigated the expression of severe acute respiratory syndrome coronavirus 2 (SAR-CoV-2) receptor angiotensin I-converting enzyme 2 (ACE2) and the cellular protease transmembrane serine protease 2 (TMPRSS2) and their associations with prognosis in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). We found that there are significant differences in susceptibility to SAR-CoV-2 among each age stages of individuals with the expression of ACE2. ACE2 was also high expressed in LUAD and LUSC, and this suggests that COVID-19 patients with lung cancers are susceptible to SAR-CoV-2 infection. Our data showed the differential gene expression level and gene coexpression of ACE2 and TMPRSS2 among each subtypes and pathological stages of LUAD and LUSC and the data were verified by meta-analysis, gene expression omnibus (GEO) data and animal models results.

scholarly journals Quescin Sulfhydryl Oxidase 1 (QSOX1) Secreted by Lung Cancer Cells Promotes Cancer Metastasis

2018 ◽  
Author(s):  
Hye-Jin Sung ◽  
Jung-Mo Ahn ◽  
Yeon-Hee Yoon ◽  
Sang-su Na ◽  
Young-Jin Choi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Cancer Tissue ◽  
Sulfhydryl Oxidase ◽  
Lung Cancers ◽  
Normal Tissues ◽  
Cancer Tissues

As lung cancer shows the highest mortality in cancer related death, serum biomarkers are demanded for the lung cancer diagnosis and its treatment. To discover lung cancer protein biomarkers, secreted proteins from primary cultured lung cancer and adjacent normal tissues from patients were subjected to LC/MS-MS proteomic analysis. Quescin sulfhydryl oxidase(QSOX1) was selected as a biomarker candidate from the proteins enriched in the secretion of lung cancer cells. QSOX1levels were higher in 82% (51 of 62 tissues) of lung cancer tissues compared to adjacent normal tissues. Importantly, QSOX1 serum levels were significantly higher in cancer patients (p<0.05, AUC=0.89), when measured by multiple reaction monitoring(MRM). Higher levels of QSOX1 are also uniquely detected in lung cancer tissues among several other solid cancers by immunohistochemistry. QSOX1 knock-downed Lewis lung cancer (LLC) cells was less viable from oxidative stress and had reduced migration and invasion. In addition, LLC mouse models with QSOX1 knock-down also proved that QSOX1 functions in promoting cancer metastasis. In conclusion, QSOX1 might be a lung cancer tissue-derived biomarker and involved in the promotion of lung cancers, and thus can be a therapeutic target for lung cancers.

scholarly journals Prognostic values, ceRNA network, and immune regulation function of SDPR in KRAS-mutant lung cancer

2020 ◽  
Author(s):  
Xiaoqing Luo ◽  
Shunli Peng ◽  
Sijie Ding ◽  
Qin Zeng ◽  
Rong Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint ◽  
Cox Regression ◽  
Tissue Array ◽  
Lung Cancers ◽  
Cox Regression Analysis ◽  
Immune Checkpoint Molecules ◽  
Cerna Network ◽  
Kaplan Meier ◽  
Infiltration Models

Abstract Background: Serum Deprivation Protein Response (SDPR) plays an important role in formation of pulmonary alveoli. However, the function and values of SDPR in lung cancer remain unknown. We explored prognostic value, expression pattern, and biological function of SDPR in non-small cell lung cancer (NSCLC) and KRAS-mutant lung cancers. Methods: SDPR expression was evaluated by quantitative real-time PCR (RT-qPCR), immunohistochemistry (IHC), and Western blot on human NSCLC cells, lung adenocarcinoma tissue array, KRAS-mutant transgenic mice, TCGA, and GEO datasets. Prognostic values of SDPR were evaluated by Kaplan–Meier and Cox regression analysis. Bioinformatics implications of SDPR including SDPR-combined transcription factors (TFs) and microRNAs were predicted. In addition, correlations between SDPR, immune checkpoint molecules, and tumor infiltration models were illustrated. Results: SDPR expression was downregulated in tumor cells and tissues. Low SDPR expression was an independent factor that correlated with shorter overall survival of patients both in lung cancer and KRAS-mutant subgroups. Meanwhile, ceRNA network was constructed to clarify the regulatory and biological functions of SDPR. Negative correlations were found between SDPR and immune checkpoint molecules (PD-L1, TNFRSF18, TNFRSF9, and TDO2). Moreover, diversity immune infiltration models were observed in NSCLC with different SDPR expression and copy number variation (CNV) patterns. Conclusions: This study elucidated regulation network of SDPR in KRAS-mutant NSCLC, and illustrated correlations between low SDPR expression and suppressed immune system, unfolding a prognostic factor and potential target for the treatment of lung cancer, especially for KRAS-mutant NSCLC.

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