YAP mediates the positive regulation of hnRNPK on the lung adenocarcinoma H1299 cell growth

2019 ◽  
Vol 51 (7) ◽  
pp. 677-687
Author(s):  
Lipei Xu ◽  
Tingting Zhang ◽  
Wensi Huang ◽  
Xiaohui Liu ◽  
Junlei Lu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Growth ◽  
Lung Adenocarcinoma ◽  
Molecular Mechanisms ◽  
Contact Inhibition ◽  
Negative Regulator ◽  
Cell Contact ◽  
Reporter System ◽  
H1299 Cell ◽  
Multifunctional Protein

AbstractLung cancer is the leading cause of cancer death worldwide, and non-small cell lung cancer (NSCLC) accounts for 80%–85% of diagnostic cases. The molecular mechanisms of NSCLC pathogenesis are not well understood. Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is a multifunctional protein that regulates gene expression and signal transduction and closely associated with tumorigenesis, but its mechanism of action in the pathogenesis of NSCLC is unclear. In this study, we observed that the expression pattern of hnRNPK in H1299 lung adenocarcinoma cells varied depending on the cell density in culture. Moreover, hnRNPK stimulated the ability of proliferation and colony formation of H1299 cells, which is important for the multilayered cell growth in culture. We further investigated whether there is an association between hnRNPK and the elements involved in the cell contact inhibition pathway. By using quantitative reverse transcriptase-polymerase chain reaction assay and a YAP activity reporter system, we found that hnRNPK upregulated the mRNA and protein levels and transcriptional activity of Yes-associated protein 1 (YAP), a master negative regulator of Hippo contact inhibition pathway. Furthermore, YAP knockdown with siRNA abolished the stimulatory effect of hnRNPK on H1299 cell proliferation. These results suggested that YAP could be one of the effectors of hnRNPK. Our data may provide new clues for further understanding the biological functions of hnRNPK, particularly in the context of lung adenocarcinoma oncogenesis.

Knockdown CYP2S1 inhibits lung cancer cells proliferation and migration

2021 ◽  
pp. 1-9
Author(s):  
Huan Guo ◽  
Baozhen Zeng ◽  
Liqiong Wang ◽  
Chunlei Ge ◽  
Xianglin Zuo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Lung Cancer Cells ◽  
Invasion And Migration ◽  
And Migration

BACKGROUND: The incidence of lung cancer in Yunnan area ranks firstly in the world and underlying molecular mechanisms of lung cancer in Yunnan region are still unclear. We screened a novel potential oncogene CYP2S1 used mRNA microassay and bioinformation database. The function of CYP2S1 in lung cancer has not been reported. OBJECTIVE: To investigate the functions of CYP2S1 in lung cancer. METHODS: Immunohistochemistry and Real-time PCR were used to verify the expression of CYP2S1. Colony formation and Transwell assays were used to determine cell proliferation, invasion and migration. Xenograft assays were used to detected cell growth in vivo. RESULTS: CYP2S1 is significantly up-regulated in lung cancer tissues and cells. Knockdown CYP2S1 in lung cancer cells resulted in decrease cell proliferation, invasion and migration in vitro. Animal experiments showed downregulation of CYP2S1 inhibited lung cancer cell growth in vivo. GSEA analysis suggested that CYP2S1 played functions by regulating E2F targets and G2M checkpoint pathway which involved in cell cycle. Kaplan-Meier analysis indicated that patients with high CYP2S1 had markedly shorter event overall survival (OS) time. CONCLUSIONS: Our data demonstrate that CYP2S1 exerts tumor suppressor function in lung cancer. The high expression of CYP2S1 is an unfavorable prognostic marker for patient survival.

scholarly journals MicroRNA-138 Inhibits Cell Growth, Invasion, and EMT of Non-Small Cell Lung Cancer via SOX4/p53 Feedback Loop

2018 ◽  
Vol 26 (3) ◽  
pp. 385-400 ◽  
Author(s):  
Dandan Li ◽  
Changjun He ◽  
Junfeng Wang ◽  
Yanbo Wang ◽  
Jianlong Bu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Growth ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Feedback Loop ◽  
Molecular Mechanisms ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung

Many studies have shown that downregulation of miR-138 occurs in a variety of cancers including non-small cell lung cancer (NSCLC). However, the precise mechanisms of miR-138 in NSCLC have not been well clarified. In this study, we investigated the biological functions and molecular mechanisms of miR-138 in NSCLC cell lines, discussing whether it could turn out to be a therapeutic biomarker of NSCLC in the future. In our study, we found that miR-138 is downregulated in NSCLC tissues and cell lines. Moreover, the low level of miR-138 was associated with increased expression of SOX4 in NSCLC tissues and cell lines. Upregulation of miR-138 significantly inhibited proliferation of NSCLC cells. In addition, invasion and EMT of NSCLC cells were suppressed by overexpression of miR-138. However, downregulation of miR-138 promoted cell growth and metastasis of NSCLC cells. Bioinformatics analysis predicted that SOX4 was a potential target gene of miR-138. Next, luciferase reporter assay confirmed that miR-138 could directly target SOX4. Consistent with the effect of miR-138, downregulation of SOX4 by siRNA inhibited proliferation, invasion, and EMT of NSCLC cells. Overexpression of SOX4 in NSCLC cells partially reversed the effect of miR-138 mimic. In addition, decreased SOX4 expression could increase the level of miR-138 via upregulation of p53. Introduction of miR-138 dramatically inhibited growth, invasion, and EMT of NSCLC cells through a SOX4/p53 feedback loop.

scholarly journals miR-200 deficiency promotes lung cancer metastasis by activating cancer-associated fibroblasts

2020 ◽  
Author(s):  
Bin Xue ◽  
Chen-Hua Chuang ◽  
Haydn M. Prosser ◽  
Cesar Seigi Fuziwara ◽  
Claudia Chan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Lung Cancer Mortality ◽  
Tumor Stroma ◽  
Metastatic Potential ◽  
Human Lung Cancer ◽  
Cancer Associated Fibroblasts

AbstractLung adenocarcinoma, the most prevalent lung cancer subtype, is characterized by its high propensity to metastasize. Despite the importance of metastasis in lung cancer mortality, its underlying cellular and molecular mechanisms remain largely elusive. Here, we identified miR-200 miRNAs as potent suppressors for lung adenocarcinoma metastasis. miR-200 expression is specifically repressed in mouse metastatic lung adenocarcinomas, and miR-200 decrease strongly correlates with poor patient survival. Consistently, deletion of mir-200c/141 in the KrasLSL-G12D/+; Trp53flox/flox lung adenocarcinoma mouse model significantly promoted metastasis, generating a desmoplastic tumor stroma highly reminiscent of metastatic human lung cancer. miR-200 deficiency in lung cancer cells promotes the proliferation and activation of adjacent cancer-associated fibroblasts (CAFs), which in turn elevates the metastatic potential of cancer cells. miR-200 regulates the functional interaction between cancer cells and CAFs, at least in part, by targeting Notch ligand Jagged1 and Jagged2 in cancer cells and inducing Notch activation in adjacent CAFs. Hence, the interaction between cancer cells and CAFs constitutes an essential mechanism to promote metastatic potential.

scholarly journals SLC15A4 Serves as a Novel Prognostic Biomarker and Target for Lung Adenocarcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Hui Huang ◽  
Junwei Wang ◽  
Shibin Chen ◽  
HongJiang He ◽  
Yu Shang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Clinical Outcomes ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Family Members ◽  
Human Lung Cancer ◽  
Survival Prediction ◽  
Aberrant Expression ◽  
Large Patient

BackgroundSLC15A family members are known as electrogenic transporters that take up peptides into cells through the proton-motive force. Accumulating evidence indicates that aberrant expression of SLC15A family members may play crucial roles in tumorigenesis and tumor progression in various cancers, as they participate in tumor metabolism. However, the exact prognostic role of each member of the SLC15A family in human lung cancer has not yet been elucidated.Materials and MethodsWe investigated the SLC15A family members in lung cancer through accumulated data from TCGA and other available online databases by integrated bioinformatics analysis to reveal the prognostic value, potential clinical application and underlying molecular mechanisms of SLC15A family members in lung cancer.ResultsAlthough all family members exhibited an association with the clinical outcomes of patients with NSCLC, we found that none of them could be used for squamous cell carcinoma of the lung and that SLC15A2 and SLC15A4 could serve as biomarkers for lung adenocarcinoma. In addition, we further investigated SLC15A4-related genes and regulatory networks, revealing its core molecular pathways in lung adenocarcinoma. Moreover, the IHC staining pattern of SLC15A4 in lung adenocarcinoma may help clinicians predict clinical outcomes.ConclusionSLC15A4 could be used as a survival prediction biomarker for lung adenocarcinoma due to its potential role in cell division regulation. However, more studies including large patient cohorts are required to validate the clinical utility of SLC15A4 in lung adenocarcinoma.

scholarly journals FAM83A-AS1 Promotes Tumor Progression Through MET Signaling in Lung Adenocarcinoma

2021 ◽  
Author(s):  
Shengbin Bai ◽  
Huijie Zhao ◽  
Xaofei Zeng ◽  
Baoyue Lin ◽  
Yinghan Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Molecular Mechanisms ◽  
Migration And Invasion ◽  
Functional Studies ◽  
Cycle Arrest ◽  
Elevated Expression ◽  
Lung Cancer Therapy ◽  
Prognosis Marker ◽  
Cancer Tissues

Abstract Background Studies demonstrate that long non-coding RNAs (lncRNAs) play critical roles in the occurrence and development of cancer. However, many of the molecular mechanisms underlying lncRNAs role in this process remains unclear. Methods Here, we analyzed lncRNA expression in lung cancer tissues based on RNA-Seq analysis and found that lncRNA FAM83A-AS1 was one of the top up-regulated lncRNAs in lung adenocarcinoma and elevated expression of FAM83A-AS1 was significantly associated with poor patient survival. We validated these results using RT-PCR and an independent cohort of lung cancer. Results Functional studies indicated that knockdown of FAM83A-AS1 decreased cell proliferation, colony formation, migration and invasion in H1299 and H838 lung cancer cells. Knockdown of FAM83A-AS1 induced the autophagy and cell cycle arrest at G2. Mechanistically, we found that MET, p62 and phosphor S6K proteins were decreased upon FAM83A-AS1 knockdown. Conclusion In conclusion, FAM83A-AS1 may have potential as a diagnosis/prognosis marker and its oncogenic role could lead to potential targeting for lung cancer therapy.

scholarly journals Integrated Analysis of Transcriptome and Prognosis Data Identifies FGF22 as a Prognostic Marker of Lung Adenocarcinoma

2019 ◽  
Vol 18 ◽  
pp. 153303381982731 ◽  
Author(s):  
Hong-Yan Liu ◽  
Hui Zhao ◽  
Wen-Xing Li
Keyword(s):  
Lung Cancer ◽  
Growth Factor ◽  
Lung Adenocarcinoma ◽  
Fibroblast Growth Factor ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Expression Profiles ◽  
Mapk Signaling ◽  
Integrated Analysis ◽  
Fibroblast Growth

Lung adenocarcinoma is one of the most common cancers worldwide. However, the molecular mechanisms of lung adenocarcinoma development are still unclear. This study aimed to investigate the expression profiles of anti-lung cancer target genes in different cancer stages and to explore their functions in tumor development. Lung adenocarcinoma transcriptome and clinical data were downloaded from Genomic Data Commons Data Portal, and the anti-lung cancer target genes were retrieved from the Thomson Reuters Integrity database. The results showed that 16 anti-lung target genes were deregulated in all stages. Among these target genes, fibroblast growth factor 22 showed the most important role in transcription regulatory networks. Further analysis revealed that APC, BRIP1, and PTTG1 may regulate fibroblast growth factor 22 and subsequently influence MAPK signaling pathway, Rap1 signaling pathways, and other tumorigenic processes in all stages. Moreover, high fibroblast growth factor 22 expression leads to poor overall survival (hazard ratio = 1.55, P = .019). These findings provide valuable information for the pathological research and treatment of lung adenocarcinoma. Future studies are needed to verify these results.

scholarly journals Small Cell Lung Cancer Transformation as a Resistance Mechanism to Osimertinib in Epidermal Growth Factor Receptor-Mutated Lung Adenocarcinoma: Case Report and Literature Review

2021 ◽  
Vol 11 ◽  
Author(s):  
Alessandro Leonetti ◽  
Roberta Minari ◽  
Giulia Mazzaschi ◽  
Letizia Gnetti ◽  
Silvia La Monica ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Growth ◽  
Lung Adenocarcinoma ◽  
Small Cell Lung Cancer ◽  
Cell Cultures ◽  
Cell Lung Cancer ◽  
Resistance Mechanism ◽  
Small Cell ◽  
Primary Cell ◽  
Small Cell Lung

Introduction: Small cell lung cancer (SCLC) transformation represents a mechanism of resistance to osimertinib in EGFR-mutated lung adenocarcinoma, which dramatically impacts patients' prognosis due to high refractoriness to conventional treatments.Case Description: We present the case of a patient who developed a SCLC phenotypic transformation as resistance mechanism to second-line osimertinib for T790M-positive EGFR-mutated NSCLC. Our patient received platinum–etoposide doublet following SCLC switch and achieved a modest clinical benefit which lasted 4 months. NGS and IHC analyses for p53 and Rb were performed on subsequent liver biopsies, revealing baseline TP53 mutation and complete absence of p53 and Rb expression. Primary cell cultures were established following a liver biopsy at the time of SCLC transformation, and drug sensitivity assays showed meaningful cell growth inhibition when osimertinib was added to platinum–etoposide compared with control (p < 0.05). A review of the current literature regarding SCLC transformation after failure of osimertinib was performed.Conclusions: Based on retrospective data available to date, platinum–etoposide chemotherapy is the preferred treatment choice in the occurrence of SCLC transformation after osimertinib failure. The extension of osimertinib in combination with chemotherapy in the occurrence of SCLC transformation as resistance mechanism to osimertinib is a matter of debate. The combination of osimertinib and platinum–etoposide was effective in inhibiting cell growth in our primary cell cultures. Clinical studies are needed to further explore this combination in the occurrence of SCLC transformation as a resistance mechanism to osimertinib.

scholarly journals Expression and Prognostic Significance of the Nicotinic Receptor Cluster on 15q25 about CHRNA5 and PSMA4 mRNA in Lung Adenocarcinoma Utilizing TCGA Datasets

2020 ◽  
Author(s):  
Yuxiu Wang ◽  
Xiaolin Wang ◽  
Liping Wang ◽  
Jianjun Gu ◽  
Daohui Gong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Excision Repair ◽  
Association Studies ◽  
Prognostic Significance ◽  
Enrichment Analysis ◽  
Smoking History ◽  
Genome Wide Association Studies ◽  
H1299 Cell ◽  
Normal Tissues

Abstract Background: Genome-wide association studies of lung cancer have shown a common variation at 15q24-25.1 as a determinant of risk, but the role of specific genes has not been proven. This study aims to explore the expression of mutations and the prognostic significance of 15q25 (CHRNA5 and PSMA4) mRNA in lung adenocarcinoma (LAC) based on immunohistochemistry, TCGA and bioinformatics. Methods: The expression of mutations on chromosome 15q25 of 576 primary LAC patients was selected and survival and gene expression data were extracted from TCGA. The relationship between expression of genes on 15q25 and clinical and prognostic Significance of LAC. An experiment with Beas-2b, A549 and H1299 cell lines was performed to further prove the difference in CHRNA5 and PSMA4 expression between lung cancer and normal cells. Immunohistochemistry data of CHRNA5 and PSMA4 were detected in LAC and normal tissues from 122 patients. Finally, Gene enrichment analysis (GSEA) was conducted to predict the regulatory genes of CHRNA5 and PSMA4. Results: CHRNA5 and PSMA4 are frequently mutated in TCGA (CHRNA5, 1.7%; PSMA4, 1.3%). Besides, the expression of CHRNA5 and PSMA4 was obviously higher in A549 and H1299 cells. And the immunohistochemical staining revealed that the levels of CHRNA5 and PSMA4 were considerably higher in the LAC group than in the normal group. Meanwhile, there was a significant association between high CHRNA5 expression and smoking history (P=0.011), smoking history pack year value (P=0.010). Furthermore, there was a significant correlation between CHRNA5 and PSMA4 expression levels and prognosis (P=0.003; P=0.008), and between higher expression and worse prognosis. GSEA results suggested that between samples with high CHRNA5 and PSMA4 expression were respectively enriched to cell cycle, base excision repair, oxidative phosphorylation, protein export, and aminoacyl tRNA biosynthesis, among others. Conclusions: CHRNA5 and PSMA4 mRNA expression has a significant impact on the clinical and survival of LAC, and they may be a potential target for treating patients with lung adenocarcinoma.

Molecular abnormalities in lung cancer.

1998 ◽  
Vol 16 (3) ◽  
pp. 1207-1217 ◽  
Author(s):  
R Salgia ◽  
A T Skarin
Keyword(s):  
Lung Cancer ◽  
Tumor Suppressor ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
Small Cell ◽  
Negative Regulator ◽  
Small Cell Lung ◽  
Molecular Abnormalities

PURPOSE To review several recently described molecular abnormalities in lung cancer and discuss their potential diagnostic and therapeutic relevance. DESIGN Articles were identified through a Medline search (1966 to 1997) and studies, including reviews, were cited in the references. RESULTS Molecular mechanisms altered in lung cancer include induced expression of oncogenes, such as RAS, MYC, c-erbB-2, and BCL-2, and loss of tumor-suppressor genes, such as RB, p53, and p16INK4A. RAS is a 21-kd G protein and up to 30% of adenocarcinomas show mutations in K-RAS oncogene. MYC encodes a transcriptional activator and amplification may adversely affect survival in small-cell lung cancer (SCLC). The growth factor receptor c-erbB-2 is overexpressed in up to 25% of non-small-cell lung cancer (NSCLC) cases. BCL-2, a negative regulator of apoptosis, is expressed differently in some NSCLCs. Abnormalities of RB, a key regulator of cell cycle, are detected in greater than 90% of SCLCs. There is an inverse relationship in lung cancer cells between expression of RB and p16INK4A, an upstream regulator of RB. Mutations of p53, with frequencies up to 50% in NSCLC and 80% in SCLC, can lead to loss of tumor-suppressor function, cellular proliferation, and inhibition of apoptosis. The identified molecular abnormalities in lung cancer are currently used to develop diagnostics for detecting early disease, as well as to identify targets for gene therapy. CONCLUSION Genetic abnormalities involved in the pathogenesis of lung cancer are rapidly being delineated. Understanding molecular abnormalities in lung cancer could potentially lead to earlier diagnosis and the development of novel investigational approaches to the treatment of lung cancer.

scholarly journals Inhibition of Kelch-like epichlorohydrin-related protein 1 promotes the progression and drug resistance of lung adenocarcinoma

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11908
Author(s):  
Hong Gao ◽  
Peipei Tang ◽  
Kejie Ni ◽  
Lun Zhu ◽  
Song Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Drug Resistance ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Lung Adenocarcinoma ◽  
Chemotherapy Resistance ◽  
Related Protein ◽  
H1299 Cell ◽  
Node Metastasis

Background Lung cancer is a common malignant carcinoma of respiratory system with high morbidity and mortality. Kelch-like epichlorohydrin-related protein 1 (Keap1), a member of the BTB-Kelch protein family, has been reported as an important molecule in several cancers. However, its potential role in tumor is still controversial. Here we aim to clarify the effect of Keap1 on the biological characteristics and chemotherapy resistance in lung adenocarcinoma (LUAD). Methods Immunohistochemistry was conducted to compare Keap1 expression in lung adenocarcinoma tissues and matched non-cancerous tissues, and the correlation between Keap1 expression and clinicopathological features was analyzed. Subsequently, the stable A549 and H1299 cell lines with Keap1 knockdown or overexpression were constructed using lentivirus. The roles of Keap1 on the cell proliferation, migration, invasion and drug resistance were investigated by colony formation assay, cell proliferation assay, wound scratch test, transwell invasion assay and drug sensitivity assay, respectively. Results Keap1 was lowly expressed in tumor tissues compared to matched non-cancerous tissues, and its expression was correlated with TNM stage and lymph node metastasis. Early stage (I) tumors without lymph node metastasis had higher levels of Keap1 expression compared with late-stage tumors (II, III) with the presence of lymphatic metastasis. Colony formation assays showed that Keap1 knockdown promoted the proliferation of A549 and H1299 cells, and the cell growth curves further confirmed this feature. In contrast, wound scratch and transwell invasion experiments showed that Keap1 overexpression inhibited cell migration and invasive malignancy. The IC50 for cisplatin and paclitaxel were significantly increased by Keap1 knockdown in A549 and H1299 cell lines. Conclusion Keap1 knockdown promotes tumor cell growth, proliferation, invasion, metastasis and chemotherapy resistance in LUAD. It may be a potential tumor marker to guide the staging and treatment of lung cancer.

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