scholarly journals Increased KIF15 Expression Predicts a Poor Prognosis in Patients with Lung Adenocarcinoma

2018 ◽  
Vol 51 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Yuan Qiao ◽  
Jingtao Chen ◽  
Chao Ma ◽  
Yingmin Liu ◽  
Peitong Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Lung Adenocarcinoma ◽  
Small Cell Lung Cancer ◽  
Messenger Rna ◽  
Poor Prognosis ◽  
Human Lung ◽  
Small Cell ◽  
Small Cell Lung ◽  
Protein Levels

Background/Aims: Lung cancer is the leading cause of cancer-related deaths worldwide. The outcome of patients with non-small cell lung cancer remains poor; the 5-year survival rate for stage IV non-small cell lung cancer is only 1.0%. KIF15 is a tetrameric kinesin spindle motor that has been investigated for its regulation of mitosis. While the roles of kinesin motor proteins in the regulation of mitosis and their potentials as therapeutic targets in pancreatic cancer have been described previously, the role of KIF15 in lung cancer development remains unknown. Methods: Paired lung carcinoma specimens and matched adjacent normal tissues were used for protein analysis. Clinical data were obtained from medical records. We first examined KIF15 messenger RNA expression in The Cancer Genome Atlas database, and then determined KIF15 protein levels using immunohistochemistry and western blotting. Differences between the groups were analyzed using repeated measures analysis of variance. Overall survival was analyzed using the Kaplan–Meier method. Cell-cycle and proliferation assays were conducted using A549, NCI-H1299, and NCI-H226 cells. Results: KIF15 was significantly upregulated at both the messenger RNA and protein levels in human lung tumor tissues. In patients with lung adenocarcinoma, KIF15 expression was positively associated with disease stages; high KIF15 expression predicted a poor prognosis. KIF15 knockdown using short hairpin RNA in two human lung adenocarcinoma cell lines induced G1/S phase cell cycle arrest and inhibited cell growth, but there was no effect in human lung squamous cell carcinoma. Conclusion: Our findings show that KIF15 is involved in lung cancer carcinogenesis. KIF15 could therefore serve as a specific prognostic marker for patients with lung adenocarcinoma.

scholarly journals KLF8 overexpression promotes the growth of human lung cancer cells by promoting the expression of JMJD2A

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Dongjie Ma ◽  
Hongsheng Liu ◽  
Yingzhi Qin ◽  
Zhenhuan Tian ◽  
Shanqing Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Colony Formation ◽  
Human Lung ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Small Cell Lung

Abstract Background Non-small-cell lung cancer (lung cancer) has become one of the leading causes worldwide and the underlying mechanism is not fully understood. The transcriptional factor Kruppel like factor 8 (KLF8) is involved in the initiation, progression, transformation, and metastasis of diverse cancers. However, the roles of KLF8 in human non-small cell lung cancer remain unknown. Methods CCK-8 kit and colony formation assay were performed to determine the cell growth of lung cancer cells. Flow cytometry analysis was used to evaluate apoptosis and cell cycle of lung cancer cells. Luciferase reporter assay was used to examine the activation of JMJD2A promoter by KLF8. Chromatin immunoprecipitation assay was performed to evaluate the binding of KLF8 to JMJD2A promoter. Western blot and polymerase chain reaction were applied to analyze the expression of interested genes. Results The mRNA and protein levels of KLF8 in human non-small cell lung cancer tissues were overexpressed compared with the non-cancer tissues. KLF8 was knocked down with lentivirus-mediated short-hairpin RNA (shRNA) in human lung cancer cells (A549 and H1299 cells). The phenotypic results showed that KLF8 knockdown decreased the proliferation rate and colony formation of lung cancer cells. By contrast, lentivirus-mediated KLF8 overexpression promoted the growth of lung cancer cells (A549 and H1299 cells) and non-cancerous bronchial epithelial cell line BEAS-2B. Next, we showed that KLF8 regulated cell cycle at the G0 phase but not regulates cellular apoptosis of lung cancer cells. KLF8 regulated the expression of the cell cycle regulators P21 and CDK4 in a JMJD2A-dependent manner and JMJD2A knockdown significantly blocked the functions of KLF8 in regulating cell cycle and proliferation of lung cancer cells. Finally, we observed that KLF8 bound the promoter of JMJD2A and facilitated the expression of JMJD2A. Conclusions Our evidence demonstrated that KLF8 upregulation in human lung cancer promotes the cell proliferation and colony formation of lung cancer cells. KLF8 binds to the promoter of JMJD2A and subsequently regulates the expression of P21 and CDK4, which contributes to the regulation of cell cycle by KLF8. KLF8 may serve as a target for the treatment of human lung cancer.

scholarly journals Cell division cycle 20 overexpression predicts poor prognosis for patients with lung adenocarcinoma

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769223 ◽  
Author(s):  
Run Shi ◽  
Qi Sun ◽  
Jing Sun ◽  
Xin Wang ◽  
Wenjie Xia ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Division ◽  
Lung Adenocarcinoma ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Tumor Size ◽  
Poor Prognosis ◽  
Small Cell ◽  
Cell Division Cycle ◽  
Small Cell Lung

The cell division cycle 20, a key component of spindle assembly checkpoint, is an essential activator of the anaphase-promoting complex. Aberrant expression of cell division cycle 20 has been detected in various human cancers. However, its clinical significance has never been deeply investigated in non-small-cell lung cancer. By analyzing The Cancer Genome Atlas database and using some certain online databases, we validated overexpression of cell division cycle 20 in both messenger RNA and protein levels, explored its clinical significance, and evaluated the prognostic role of cell division cycle 20 in non-small-cell lung cancer. Cell division cycle 20 expression was significantly correlated with sex (p = 0.003), histological classification (p < 0.0001), and tumor size (p = 0.0116) in non-small-cell lung cancer patients. In lung adenocarcinoma patients, overexpression of cell division cycle 20 was significantly associated with bigger primary tumor size (p = 0.0023), higher MKI67 level (r = 0.7618, p < 0.0001), higher DNA ploidy level (p < 0.0001), and poor prognosis (hazard ratio = 2.39, confidence interval: 1.87–3.05, p < 0.0001). However, in lung squamous cell carcinoma patients, no significant association of cell division cycle 20 expression was observed with any clinical parameter or prognosis. Overexpression of cell division cycle 20 is associated with poor prognosis in lung adenocarcinoma patients, and its overexpression can also be used to identify high-risk groups. In conclusion, cell division cycle 20 might serve as a potential biomarker for lung adenocarcinoma patients.

scholarly journals Screening prognostic markers for non-small cell lung cancer based on data mining and bioinformatics analysis

2020 ◽  
Author(s):  
Bin Han ◽  
Kaushik Chandra Aman ◽  
Dongqing Wei ◽  
Shulin Zhang ◽  
Minjie Meng
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Small Cell Lung Cancer ◽  
Differentially Expressed Genes ◽  
Cell Lung Cancer ◽  
Poor Prognosis ◽  
Prognostic Markers ◽  
Small Cell ◽  
Differentially Expressed ◽  
Small Cell Lung

Abstract Background At present, non-small cell lung cancer has a high morbidity and mortality, and the recurrence and metastasis situation is serious. It is impossible to accurately predict the prognosis of cancer patients clinically. Biomarker is a kind of biomolecule with wide application prospects, and its potential in cancer prognosis is gradually revealed, and it is expected to be applied clinically. Results We integrated four gene expression profiles (GSE19188, GSE19804, GSE101929 and GSE18842) from the GEO database and screened the commonly differentially expressed genes using the GEO2R online tool. We screened 952 commonly differentially expressed genes. Gene ontology analysis showed that CDEGs were mainly enriched in biological processes such as cell adherin, angiogenesis and positive regulation of angiogenesis, and KEGG pathways such as ECM-receptor interaction and cell adherin molecules (CAMs). Up-regulation of G2 and S phase-expressed protein 1(GTSE1) expression is associated with poor prognosis of lung adenocarcinoma(LADE) and lung squamous cell carcinoma(LUSC). Up-regulation of Neuromedin-U(NMU) expression, down-regulation of Proto-oncogene c-Fos(FOS) and Cyclin-dependent kinase inhibitor 1C(CDKN1C) is only associated with poor prognosis of LADE. Conclusions We believe that GTSE1, NMU, FOS, and CDKN1C have potential application value as prognostic markers for lung adenocarcinoma, and are of great significance for lung adeno carcinoma efficacy evaluation and relapse monitoring. At the same time, GTSE1 may also be used as a new target for cancer treatment New ways.

LIFE SPAN PREDICTION AT METASTATIC NON-SMALL CELL LUNG CANCER

2018 ◽  
Vol 64 (4) ◽  
pp. 522-527
Author(s):  
Aleksey Shutko ◽  
Viktor Mus
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Small Cell Lung Cancer ◽  
Life Span ◽  
Cell Lung Cancer ◽  
Poor Prognosis ◽  
Small Cell ◽  
Hemopoietic Stem Cells ◽  
Small Cell Lung ◽  
Individual Life

Individual parameters of circulating hemopoietic stem cells (HSC) lymphoid origin were measured by cytofluorometry before treatment of patients with metastatic non-small cell lung cancer and were retrospectively compared with individual life span's (LS). The possibility of poor prognosis of treatment's results (LS

scholarly journals Diethylstilbestrol, a Novel ANO1 Inhibitor, Exerts an Anticancer Effect on Non-Small Cell Lung Cancer via Inhibition of ANO1

2021 ◽  
Vol 22 (13) ◽  
pp. 7100
Author(s):  
Yohan Seo ◽  
Sung Baek Jeong ◽  
Joo Han Woo ◽  
Oh-Bin Kwon ◽  
Sion Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
High Throughput Screening ◽  
Fluorescent Protein ◽  
Yellow Fluorescent Protein ◽  
Small Cell ◽  
Channel Activity ◽  
Small Cell Lung ◽  
Protein Levels

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related mortality; thus, therapeutic targets continue to be developed. Anoctamin1 (ANO1), a novel drug target considered for the treatment of NSCLC, is a Ca2+-activated chloride channel (CaCC) overexpressed in various carcinomas. It plays an important role in the development of cancer; however, the role of ANO1 in NSCLC is unclear. In this study, diethylstilbestrol (DES) was identified as a selective ANO1 inhibitor using high-throughput screening. We found that DES inhibited yellow fluorescent protein (YFP) fluorescence reduction caused by ANO1 activation but did not inhibit cystic fibrosis transmembrane conductance regulator channel activity or P2Y activation-related cytosolic Ca2+ levels. Additionally, electrophysiological analyses showed that DES significantly reduced ANO1 channel activity, but it more potently reduced ANO1 protein levels. DES also inhibited the viability and migration of PC9 cells via the reduction in ANO1, phospho-ERK1/2, and phospho-EGFR levels. Moreover, DES induced apoptosis by increasing caspase-3 activity and PARP-1 cleavage in PC9 cells, but it did not affect the viability of hepatocytes. These results suggest that ANO1 is a crucial target in the treatment of NSCLC, and DES may be developed as a potential anti-NSCLC therapeutic agent.

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