scholarly journals RNA-seq-Based Screening in Coal Dust-Treated Cells Identified PHLDB2 as a Novel Lung Cancer-Related Molecular Marker

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Deyong Ge ◽  
Yuhan Shao ◽  
Mengjie Wang ◽  
Huihui Tao ◽  
Min Mu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Coal Dust ◽  
Critical Role ◽  
Differentially Expressed Gene ◽  
Disease Diagnosis ◽  
Rna Seq ◽  
Cancer Dataset ◽  
High Incidence ◽  
Raw264.7 Cell

Lung cancer is one of the most serious leading cancers with high incidence globally. Identifying molecular markers is key for disease diagnosis and treatment. Coal dust might be important triggering factors in disease development. Here, we first performed RNA-seq-based screening in coal dust treated and nontreated RAW264.7 cell lines. PHLDB2 was found to be the top differentially expressed gene. By retrieving TCGA lung cancer dataset, we observed that PHLDB2 showed upregulations in males and smoker patients. Patients with lower PHLDB2 expression survived longer than those with higher expressions. Furthermore, PHLDB2 was negatively correlated with EMT makers, and a total of 2.74% mutation rate were observed in 1,059 patients. This finding highlights the critical role of PHLDB2 in lung cancer development. PHLDB2 might be a molecular maker for disease diagnosis or treatment.

scholarly journals Targeting HSPA1A in ARID2-deficient lung adenocarcinoma

2021 ◽  
Author(s):  
Xue Wang ◽  
Yuetong Wang ◽  
Zhaoyuan Fang ◽  
Hua Wang ◽  
Jian Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Genetically Engineered ◽  
Malignant Progression ◽  
Murine Models ◽  
Rna Seq ◽  
Potential Therapeutic Target ◽  
Lung Cancers ◽  
Integrative Analyses

Abstract Somatic mutations of the chromatin remodeling gene ARID2 are observed in about 7% of human lung adenocarcinoma (LUAD). However, the role of ARID2 in the pathogenesis of LUAD remains largely unknown. Here we find that ARID2 expression is decreased during the malignant progression of both human and mice LUAD. Using two KrasG12D-based genetically engineered murine models (GEMM), we demonstrate that ARID2 knockout significantly promotes lung cancer malignant progression and shortens the overall survival. Consistently, ARID2 knockdown significantly promotes cell proliferation in human and mice lung cancer cells. Through integrative analyses of Chip-Seq and RNA-Seq data, we find that Hspa1a is up-regulated by Arid2 loss. Knockdown of Hspa1a specifically inhibits malignant progression of Arid2-deficient but not Arid2-wt lung cancers in both cell lines as well as animal models. Treatment with Hspa1a inhibitor could significantly inhibit the malignant progression of lung cancer with Arid2 deficiency. Together, our findings establish ARID2 as an important tumor suppressor in LUAD with novel mechanistic insights, and further identify HSPA1A as a potential therapeutic target in ARID2-deficient LUAD.

scholarly journals Requirement for PKC Epsilon in Kras-Driven Lung Tumorigenesis

2020 ◽  
Author(s):  
Rachana Garg ◽  
Mariana Cooke ◽  
Shaofei Wang ◽  
Fernando Benavides ◽  
Martin C. Abba ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Cancer Therapeutics ◽  
Rna Seq ◽  
Lung Tumorigenesis ◽  
Mechanistic Analysis ◽  
Oncogenic Driver ◽  
Histological Form

ABSTRACTNon-small cell lung cancer (NSCLC), the most frequent subtype of lung cancer, remains a highly lethal malignancy and one of the leading causes of cancer deaths worldwide. Mutant KRAS is the prevailing oncogenic driver of lung adenocarcinoma, the most common histological form of NSCLC. In this study, we examined the role of PKCε, an oncogenic kinase highly expressed in NSCLC and other cancers, in KRAS-driven tumorigenesis. Notably, database analysis revealed an association between PKCε expression and poor outcome in lung adenocarcinoma patients specifically having KRAS mutation. By generating a PKCε-deficient, conditionally activatable allele of oncogenic Kras (LSL-KrasG12D;PKCε−/− mice) we were able to demonstrate the requirement of PKCε for Kras-driven lung tumorigenesis in vivo, which is consistent with the impaired transformed growth observed in PKCε-deficient KRAS-dependent NSCLC cells. Moreover, PKCε-knockout mice were found to be less susceptible to lung tumorigenesis induced by benzo[a]pyrene, a carcinogen that induces mutations in Kras. Mechanistic analysis using RNA-Seq revealed little overlapping for PKCε and KRAS in the control of genes/biological pathways relevant in NSCLC, suggesting that a permissive role of PKCε in KRAS-driven lung tumorigenesis may involve non-redundant mechanisms. Our results thus highlight the relevance and potential of targeting PKCε for lung cancer therapeutics.

scholarly journals Critical Role of Gα12 and Gα13 for Human Small Cell Lung Cancer Cell Proliferation In vitro and Tumor Growth In vivo

2010 ◽  
Vol 16 (5) ◽  
pp. 1402-1415 ◽  
Author(s):  
Marius Grzelinski ◽  
Olaf Pinkenburg ◽  
Thomas Büch ◽  
Maike Gold ◽  
Stefanie Stohr ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Critical Role ◽  
Small Cell ◽  
Cancer Cell Proliferation ◽  
Lung Cancer Cell ◽  
Small Cell Lung ◽  
Proliferation In Vitro

A Critical Role of Luteolin-Induced Reactive Oxygen Species in Blockage of Tumor Necrosis Factor-Activated Nuclear Factor-κB Pathway and Sensitization of Apoptosis in Lung Cancer Cells

2007 ◽  
Vol 71 (5) ◽  
pp. 1381-1388 ◽  
Author(s):  
Wei Ju ◽  
Xia Wang ◽  
Honglian Shi ◽  
Wenshu Chen ◽  
Steven A. Belinsky ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Reactive Oxygen Species ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Critical Role ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Necrosis Factor

scholarly journals Haemocytes are critical for Drosophila melanogaster post-embryonic development, independent of control of the microbiota

2021 ◽  
Author(s):  
Holly N Stephenson ◽  
Robert Streeck ◽  
Alf Herzig
Keyword(s):  
Embryonic Development ◽  
Adult Development ◽  
Critical Role ◽  
Rna Seq ◽  
Genetic Rescue ◽  
Germ Free ◽  
Drosophila Model ◽  
Axenic Conditions ◽  
Driver Line

Proven roles for haemocytes (blood cells) have expanded beyond the control of infections in Drosophila. Despite this, the critical role of haemocytes in post-embryonic development has long been thought to be limited to control of microorganisms during metamorphosis. This has previously been shown by rescue of adult development in haemocyte-ablation models under germ-free conditions. Here we show that haemocytes have a critical role in post-embryonic development beyond their ability to control the microbiota. Using a newly generated, strong haemocyte-specific driver line for the GAL4/UAS system, we show that specific ablation of haemocytes is pupal lethal, even under axenic conditions. Genetic rescue experiments prove that this is a haemocyte-specific phenomena. RNA-seq data suggests that dysregulation of the midgut is a critical consequence of haemocyte ablation. We believe this novel role of haemocytes during metamorphosis is a major finding for the field. This is an exciting new Drosophila model to study the precise mechanisms in which haemocytes regulate tissue development, findings from which could have far reaching implications beyond invertebrate biology.

scholarly journals Circular RNA circFGFR1 promotes progression and anti-PD-1 resistance by sponging miR-381-3p in non-small cell lung cancer cells

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Peng-Fei Zhang ◽  
Xu Pei ◽  
Ke-Sang Li ◽  
Li-Na Jin ◽  
Fei Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Immune Evasion ◽  
Critical Role ◽  
Circular Rna ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

Abstract Background Immune system evasion, distance tumor metastases, and increased cell proliferation are the main reasons for the progression of non-small cell lung cancer (NSCLC) and the death of NSCLC patients. Dysregulation of circular RNAs plays a critical role in the progression of NSCLC; therefore, further understanding the biological mechanisms of abnormally expressed circRNAs is critical to discovering novel, promising therapeutic targets for NSCLC treatment. Methods The expression of circular RNA fibroblast growth factor receptor 1 (circFGFR1) in NSCLC tissues, paired nontumor tissues, and cell lines was detected by RT-qPCR. The role of circFGFR1 in NSCLC progression was assessed both in vitro by CCK-8, clonal formation, wound healing, and Matrigel Transwell assays and in vivo by a subcutaneous tumor mouse assay. In vivo circRNA precipitation, RNA immunoprecipitation, and luciferase reporter assays were performed to explore the interaction between circFGFR1 and miR-381-3p. Results Here, we report that circFGFR1 is upregulated in NSCLC tissues, and circFGFR1 expression is associated with deleterious clinicopathological characteristics and poor prognoses for NSCLC patients. Forced circFGFR1 expression promoted the migration, invasion, proliferation, and immune evasion of NSCLC cells. Mechanistically, circFGFR1 could directly interact with miR-381-3p and subsequently act as a miRNA sponge to upregulate the expression of the miR-381-3p target gene C-X-C motif chemokine receptor 4 (CXCR4), which promoted NSCLC progression and resistance to anti-programmed cell death 1 (PD-1)- based therapy. Conclusion Taken together, our results suggest the critical role of circFGFR1 in the proliferation, migration, invasion, and immune evasion abilities of NSCLC cells and provide a new perspective on circRNAs during NSCLC progression.

Abstract A38: A critical role of Wnt5a-Axin2 axis in small-cell lung cancer development

2020 ◽  
Author(s):  
Kee-Beom Kim ◽  
Dong-Wook Kim ◽  
Youngchul Kim ◽  
Jae-Il Park ◽  
Kwon-Sik Park
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Critical Role ◽  
Small Cell ◽  
Cancer Development ◽  
Small Cell Lung

scholarly journals Interplay between Cellular and Molecular Inflammatory Mediators in Lung Cancer

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Mario Orozco-Morales ◽  
Giovanny Soca-Chafre ◽  
Pedro Barrios-Bernal ◽  
Norma Hernández-Pedro ◽  
Oscar Arrieta
Keyword(s):  
Lung Cancer ◽  
Immune Suppression ◽  
Critical Role ◽  
Inflammatory Cells ◽  
T Cell Response ◽  
Invasion And Metastasis ◽  
Remodeling Of Extracellular Matrix ◽  
Tumor Associated Neutrophils

Inflammation is a component of the tumor microenvironment and represents the 7th hallmark of cancer. Chronic inflammation plays a critical role in tumorigenesis. Tumor infiltrating inflammatory cells mediate processes associated with progression, immune suppression, promotion of neoangiogenesis and lymphangiogenesis, remodeling of extracellular matrix, invasion and metastasis, and, lastly, the inhibition of vaccine-induced antitumor T cell response. Accumulating evidence indicates a critical role of myeloid cells in the pathophysiology of human cancers. In contrast to the well-characterized tumor-associated macrophages (TAMs), the significance of granulocytes in cancer has only recently begun to emerge with the characterization of tumor-associated neutrophils (TANs). Recent studies show the importance of CD47 in the interaction with macrophages inhibiting phagocytosis and promoting the migration of neutrophils, increasing inflammation which can lead to recurrence and progression in lung cancer. Currently, therapies are targeted towards blocking CD47 and enhancing macrophage-mediated phagocytosis. However, antibody-based therapies may have adverse effects that limit its use.

scholarly journals ADAMTSL4, a Secreted Glycoprotein, Is a Novel Immune-Related Biomarker for Primary Glioblastoma Multiforme

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Zheng Zhao ◽  
Ke-Nan Zhang ◽  
Rui-Chao Chai ◽  
Kuan-Yu Wang ◽  
Ruo-Yu Huang ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Critical Role ◽  
The Body ◽  
Rna Seq ◽  
Clinicopathologic Characteristics ◽  
Who Grade ◽  
Primary Glioblastoma ◽  
Potential Marker ◽  
Independent Indicator

Background. Researches on immunotherapy of glioblastoma multiforme (GBM, WHO grade IV) have increased exponentially in recent years. As a targeted therapy, a series of biomarkers have been identified in local tumor tissue, while circulating marker which could be detected in the body fluids is still lacking. ADAMTSL4, a secreted glycoprotein, was earlier found to play a critical role in a prognostic signature for primary GBM (pGBM). We aimed to investigate the role of ADAMTSL4 at transcriptome level and its relationship with clinical practice in pGBM. Methods. A cohort of 88 pGBM patients with RNA-seq data from the Chinese Glioma Genome Atlas (CGGA) was analyzed, and 168 pGBM patients from TCGA were included as validation. Several bioinformatic methods and predictive tools were applied to investigate the ADAMTSL4-associated immune microenvironment status. Results. We found that ADAMTSL4 was enriched in GBM (WHO grade IV), especially for those with IDH1/2 wild-type and MGMT unmethylated groups. According to the TCGA classification scheme, ADAMTSL4 can act as a potential marker for subtypes with poorer prognosis. Bioinformatic analyses revealed that ADAMTSL4 was significantly correlated to the immune-related processes in GBM (WHO grade IV), especially representing the infiltration of immune cells and complicated tumor microenvironment. Clinically, high expression of ADAMTSL4 was an independent indicator for poor prognosis. Conclusion. The expression of ADAMTSL4 is closely related to the clinicopathologic characteristics of pGBM. Meanwhile, it may play a critical role in immune-related processes. As a secreted glycoprotein, ADAMTSL4 is a promising circulating biomarker for pGBM, deserving further investigations.

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