Abstract 4883: Differences in epigenetic patterns ofHOXgenes in normal lung and Non-small cell lung cancer

2010 ◽  
Author(s):  
Borum Lee ◽  
Sung-Min Chun ◽  
Min-Young Jin ◽  
Se Jin Jang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Normal Lung ◽  
Small Cell Lung ◽  
Epigenetic Patterns

The Key microRNAs Regulated the Development of Non-small Cell Lung Cancer by Targeting TGF-β-induced epithelial–mesenchymal Transition

2019 ◽  
Vol 22 (4) ◽  
pp. 238-244 ◽  
Author(s):  
Gang Chen ◽  
Bo Ye
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nsclc Cell ◽  
Normal Lung ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Mesenchymal Transition

Purpose: Epithelial-to-Mesenchymal Transition (EMT) was reported to play a key role in the development of Non-Small Cell Lung Cancer (NSCLC). The process of EMT is regulated by the changes of miRNAs expression. However, it is still unknown which miRNA changed the most in the process of canceration and whether these changes played a role in tumor development. Methods: A total of 36 SCLC patients treated in our hospital between 11th, 2015 and 10th, 2017 were enrolled. The samples of cancer tissues and paracancer tissues of patients were collected and analyzed. Then, the miRNAs in normal lung cells and NSCLC cells were also analyzed. In the presence of TGF-β, we transfected the miRNA mimics or inhibitor into NSCLC cells to investigate the role of the significantly altered miRNAs in cell migration and invasion and in the process of EMT. Results: MiR-330-3p was significantly up-regulated in NSCLC cell lines and tissues and miRNA- 205 was significantly down-regulated in NSCLC cell lines and NSCLC tissues. Transfected miRNA-205 mimics or miRMA-330-3p inhibitor inhibited the migration and invasion of NCIH1975 cell and restrained TGF-β-induced EMT in NSCLC cells. Conclusion: miRNA-330-3p and miRNA-205 changed the most in the process of canceration in NSCLC. Furthermore, miR-330-3p promoted cell invasion and metastasis in NSCLC probably by promoting EMT and miR-205 could restrain NSCLC likely by suppressing EMT.

scholarly journals Kinesin superfamily protein 21B acts as an oncogene in non-small cell lung cancer

2020 ◽  
Author(s):  
Zhi-Gang Sun ◽  
Feng Pan ◽  
Jing-Bo Shao ◽  
Qian-Qian Yan ◽  
Lu Lu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Nude Mice ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Normal Lung ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Kinesin Superfamily

Abstract Background: Kinesin superfamily proteins (KIFs) serve as microtubule-dependent molecular motors, and are involved in the progression of many malignant tumors. In this study, we aimed to investigate the expression pattern and precise role of kinesin family member 21B (KIF21B) in non-small cell lung cancer (NSCLC). Methods: KIF21B expression in 72 cases of NSCLC tissues was measured by immunohistochemical staining (IHC). We used shRNA-KIF21B interference to silence KIF21B in NSCLC H1299 and A549 cells and normal lung epithelial bronchus BEAS-2B cells. The biological roles of KIF21B in the growth and metastasis abilities of NSCLC cells were measured by Cell Counting Kit-8 (CCK8), colony formation and Hoechst 33342/PI, wound-healing, and Transwell assays, respectively. Expression of apoptosis-related proteins was determined using western blot. The effect of KIF21B on tumor growth in vivo was examined using nude mice model. Results: KIF21B was up-regulated in NSCLC tissues, and correlated with pathological lymph node and pTNM stage, its high expression was predicted a poor prognosis of patients with NSCLC. Silencing of KIF21B mediated by lentivirus-delivered shRNA significantly inhibited the proliferation ability of H1299 and A549 cells. KIF21B knockdown increased apoptosis in H1299 and A549 cells, down-regulated the expression of Bcl-2 and up-regulated the expression of Bax and active Caspase 3. Moreover, KIF21B knockdown decreased the level of phosphorylated form of Akt (p-Akt) and Cyclin D1 expression in H1299 and A549 cells. In addition, silencing of KIF21B impeded the migration and invasion of H1299 and A549 cells. Further, silencing of KIF 21B dramatically inhibited xenograft growth in BALB/c nude mice. However, silencing of KIF21B did not affect the proliferation, migration and invasion of BEAS-2B cells.Conclusions: These results reveal that KIF21B is up-regulated in NSCLC and acts as an oncogene in the growth and metastasis of NSCLC, which may function as a potential therapeutic target and a prognostic biomarker for NSCLC.

scholarly journals Identification of Gene Biomarkers for Distinguishing Small-Cell Lung Cancer from Non-Small-Cell Lung Cancer Using a Network-Based Approach

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Fei Long ◽  
Jia-Hang Su ◽  
Bin Liang ◽  
Li-Li Su ◽  
Shu-Juan Jiang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Expression Patterns ◽  
Small Cell ◽  
Normal Lung ◽  
Specific Gene ◽  
Small Cell Lung ◽  
Cancer Subtypes ◽  
Gene Modules

Lung cancer consists of two main subtypes: small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) that are classified according to their physiological phenotypes. In this study, we have developed a network-based approach to identify molecular biomarkers that can distinguish SCLC from NSCLC. By identifying positive and negative coexpression gene pairs in normal lung tissues, SCLC, or NSCLC samples and using functional association information from the STRING network, we first construct a lung cancer-specific gene association network. From the network, we obtain gene modules in which genes are highly functionally associated with each other and are either positively or negatively coexpressed in the three conditions. Then, we identify gene modules that not only are differentially expressed between cancer and normal samples, but also show distinctive expression patterns between SCLC and NSCLC. Finally, we select genes inside those modules with discriminating coexpression patterns between the two lung cancer subtypes and predict them as candidate biomarkers that are of diagnostic use.

scholarly journals A Study on Cytotoxic and Apoptotic Potential of a Triterpenoid Saponin (3-O-α-L-Arabinosyl Oleanolic Acid) Isolated fromSchumacheria castaneifoliaVahl in Human Non-Small-Cell Lung Cancer (NCI-H292) Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Sameera R. Samarakoon ◽  
Meran K. Ediriweera ◽  
Chukwumaobim Daniel Uzochukwuwulu Nwokwu ◽  
Chamara Janaka Bandara ◽  
Kamani H. Tennekoon ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Oleanolic Acid ◽  
Cell Lung Cancer ◽  
Caspase 3 ◽  
Small Cell ◽  
Normal Lung ◽  
Small Cell Lung ◽  
Cytotoxic Effects

Lung cancer is the major cause of cancer death among men. A number of natural compounds have proven to be useful in the treatmet of lung cancer. This study was aimed to determine cytotoxic and apoptotoic effects of a natural compound 3-O-α-L-arabinosyl oleanolic acid (3-O-L-AO) isolated fromSchumacheria castaneifoliain non-small-cell lung cancer (NCI-H292) cells. Cytotoxic effects of 3-O-L-AO were determined by Sulforhodamine B (SRB) assay and apoptotic effects were tested by evaluating (a) apoptotsis related morphological changes, (b) caspase 3/7 activity, and (c) expression ofBax, p53, and survivingenes. Oxidative stress markers (reactive oxygen species (ROS), glutathione-S-transferase (GST), and glutathione (GSH)) were also analysed in 3-O-L-AO treated NCI-H292 cells. 3-O-L-AO exerted potent cytotoxic effects in NCI-H292 cells while being less cytotoxic to normal lung (MRC-5) cells. Exposure to 3-O-L-AO caused upregulation ofBaxandp53and downregulation ofsurvivinin NCI-H292 cells. Activation of caspase 3/7 and morphological features related to apoptosis further confirmed 3-O-L-AO induced apoptosis. Furthermore, elevated ROS and GST levels and decreased GSH levels suggested 3-O-L-AO can induce apoptosis, possibly causing oxidative stress in NCI-H292 cells. Overall results suggest that 3-O-L-AO can be considered as an effective anticancer agent for the treatment of lung cancer.

scholarly journals Early Candidate Biomarkers of Non–Small Cell Lung Cancer Are Screened and Identified in Premalignant Lung Lesions

2016 ◽  
Vol 16 (1) ◽  
pp. 66-74 ◽  
Author(s):  
Yandong Nan ◽  
Jie Du ◽  
Lijie Ma ◽  
Hua Jiang ◽  
Faguang Jin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Cell Lung Cancer ◽  
Src Kinase ◽  
Small Cell ◽  
Normal Lung ◽  
Biological Processes ◽  
Small Cell Lung

A specific protein profile that accompanies neoplastic transformation in the premalignant airway epithelium could provide an opportunity for early diagnosis of lung cancer. The aim of this study was to screen and identify early candidate biomarkers of non–small cell lung cancer. Thirteen non–small cell lung cancer samples were obtained within 30 minutes after a surgical resection. Laser capture microdissection was performed to enrich the normal lung cell and squamous metaplasia or atypical adenomatous hyperplasia cell populations. The resulting tandem mass spectrum was automatically searched for proteins against International Protein Index (IPI) human protein database using the TurboSEQUEST searching engine. The molecular function and biological processes of identified proteins were determined based on universal bioinformatics tools. The 2 proteins of interest, focal adhesion kinase and C-terminal Src kinase, were validated using Western blot method. A total of 863 proteins were identified by automatically searching the tandem mass spectrum, among which 427 were dysregulated expression in premalignant airway epithelium compared with those of normal lung cells. The 427 proteins were mainly distributed in 24 sorts of cellular components, 22 molecular function, 15 biological processes, and 10 significant perturbations of pathways. The most significant network included 48 genes and was related to energy production, cell cytoskeleton, cell adhesion, metabolism, oxidative stress, and small molecule biochemistry. Focal adhesion kinase and C-terminal Src kinase were significantly overexpressed in premalignant lung lesion cells compared with the normal lung cells in 13 cases. We identified that there were 427 proteins involved in non–small cell lung cancer carcinogenic process and confirmed the key biological pathways in premalignant lung tissue. The significantly upregulated focal adhesion kinase and C-terminal Src kinase could be considered as molecular biomarkers for early diagnosis and prognosis of non–small cell lung cancer.

scholarly journals Interferon-gamma-inducible protein 10 (IP-10) is an angiostatic factor that inhibits human non-small cell lung cancer (NSCLC) tumorigenesis and spontaneous metastases.

1996 ◽  
Vol 184 (3) ◽  
pp. 981-992 ◽  
Author(s):  
D A Arenberg ◽  
S L Kunkel ◽  
P J Polverini ◽  
S B Morris ◽  
M D Burdick ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Lung Metastases ◽  
Small Cell ◽  
Normal Lung ◽  
Small Cell Lung ◽  
Angiogenic Activity ◽  
Human Nsclc

The success of solid tumor growth and metastasis is dependent upon angiogenesis. Neovascularization within the tumor is regulated, in part, by a dual and opposing system of angiogenic and angiostatic factors. We now report that IP-10, a recently described angiostatic factor, as a potent angiostatic factor that regulates non-small cell lung cancer (NSCLC)-derived angiogenesis, tumor growth, and spontaneous metastasis. We initially found significantly elevated levels of IP-10 in freshly isolated human NSCLC samples of squamous cell carcinoma (SCCA). In contrast, levels of IP-10 were equivalent in either normal lung tissue or adenocarcinoma specimens. The neoplastic cells in specimens of SCCA were the predominant cells that appeared to express IP-10 by immunolocalization. Neutralization of IP-10 in SCCA tumor specimens resulted in enhanced tumor-derived angiogenic activity. Using a model of human NSCLC tumorigenesis in SCID mice, we found that NSCLC tumor growth was inversely correlated with levels of plasma or tumor-associated IP-10. IP-10 in vitro functioned as neither an autocrine growth factor nor as an inhibitor of proliferation of the NSCLC cell lines. Reconstitution of intratumor IP-10 for a period of 8 wk resulted in a significant inhibition of tumor growth, tumor-associated angiogenic activity and neovascularization, and spontaneous lung metastases, whereas, neutralization of IP-10 for 10 wk augmented tumor growth. These findings support the notion that tumor-derived IP-10 is an important endogenous angiostatic factor in NSCLC.

scholarly journals The relaxin family peptide receptor 1, RXFP1, is differentially expressed in non-small cell lung cancer and associates with patient survival.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
The United States ◽  
Small Cell ◽  
Differentially Expressed ◽  
Normal Lung ◽  
Small Cell Lung ◽  
Peptide Receptor ◽  
Relaxin Family

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in the United States (1). We mined published microarray data (2, 3, 4) to identify differentially expressed genes in NSCLC. We found that the gene encoding the relaxin family peptide receptor 1, RXFP1, was among those whose expression was most different in human NSCLC tumors as compared to the lung. RXFP1 expression levels were significantly decreased in NSCLC tumors relative to normal lung tissue, and lower expression of RXFP1 in patient tumors was significantly associated with decreased overall survival. RXFP1 may be important for initiation or progression of non-small cell lung cancer in humans.

scholarly journals Epigenetic Suppression of the T-box Subfamily 2 (TBX2) in Human Non-Small Cell Lung Cancer

2019 ◽  
Vol 20 (5) ◽  
pp. 1159 ◽  
Author(s):  
Eliana Nehme ◽  
Zahraa Rahal ◽  
Ansam Sinjab ◽  
Athar Khalil ◽  
Hassan Chami ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Normal Lung ◽  
Small Cell Lung ◽  
Alveolar Cells ◽  
Expression Levels ◽  
Human Nsclc

(1) The TBX2 subfamily of transcription factors (TBXs 2, 3, 4 and 5) are markedly down-regulated in human non-small cell lung cancer (NSCLC) and exert tumor suppressor effects in lung malignancy. Yet, mechanisms underlying suppressed expression of the TBX2 subfamily in NSCLC are elusive. Here, we interrogated probable epigenetic mechanisms in suppressed expression of the TBX2 subfamily in human NSCLC. (2) TBX2 subfamily gene expression and methylation levels in NSCLC and normal lung tissues were surveyed using publicly available RNA-sequence and genome-wide methylation datasets. Methylation β-values of the four genes were statistically compared between NSCLCs and normal lung tissues, correlated with gene expression levels, and interrogated with clinicopathological variables. Expression and methylation levels of TBXs were quantified in NSCLC cells using real-time PCR and methylation-specific PCR assays, respectively. Effects of the DNA methyltransferase inhibitor 5-azacytidine (Aza) on TBX2 subfamily expression were assessed in NSCLC cells. Impact of TBX2 subfamily expression on Aza-treated cells was evaluated by RNA interference. (3) All four TBXs were significantly hypermethylated in NSCLCs relative to normal lung tissues (p < 0.05). Methylation β-values of the genes, with exception of TBX2, were significantly inversely correlated with corresponding mRNA expression levels (p < 0.05). We found no statistically significant differences in hypermethylation levels of the TBX2 subfamily by clinicopathological features including stage and tobacco history. Expression levels of the TBX genes were overall suppressed in NSCLC cells relative to normal alveolar cells. Members of the subfamily were significantly hypermethylated in all tested NSCLC cell lines relative to normal alveolar cells. Treatment with Aza induced the expression of the TBX2 subfamily concomitant with NSCLC cell growth inhibition. Further, simultaneous knockdown of the four TBX genes markedly reduced anti-growth effects of Aza in NSCLC cells. (4) Our study sheds light on new epigenetic profiles in the molecular pathogenesis of human NSCLC.

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