scholarly journals Identification by MicroRNA Analysis of Environmental Risk Factors Bearing Pathogenic Relevance in Non-Smoker Lung Cancer

2021 ◽  
Vol 11 (7) ◽  
pp. 666
Author(s):  
Alberto Izzotti ◽  
Gabriela Coronel Vargas ◽  
Alessandra Pulliero ◽  
Simona Coco ◽  
Cristina Colarossi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Environmental Factors ◽  
Dna Adducts ◽  
Human Lung ◽  
Environmental Exposures ◽  
Human Lung Cancer ◽  
Environmental Carcinogens ◽  
Lung Cancers ◽  
Car Traffic ◽  
Lung Biopsies

MicroRNA and DNA adduct biomarkers may be used to identify the contribution of environmental pollution to some types of cancers. The aim of this study was to use integrated DNA adducts and microRNAs analyses to study retrospectively the contribution of exposures to environmental carcinogens to lung cancer in 64 non-smokers living in Sicily and Catania city near to the Etna volcano. MicroRNAs were extracted from cancer lung biopsies, and from the surrounding lung normal tissue. The expression of 2549 human microRNAs was analyzed by microarray. Benzo(a)Pyrene-DNA adducts levels were analyzed in the patients’ blood by HPLC−fluorescence detection. Correlations between tetrols and environmental exposures were calculated using Pearson coefficients and regression variable plots. Compared with the healthy tissue, 273 microRNAs were downregulated in lung cancer. Tetrols levels were inversely related both with the distance from Etna and years since smoking cessation, but they were not significantly correlated to environmental exposures. The analysis of the microRNA environmental signatures indicates the contribution of environmental factors to the analyzed lung cancers in the following decreasing rank: (a) car traffic, (b) passive smoke, (c) radon, and (d) volcano ashes. These results provide evidence that microRNA analysis can be used to retrospectively investigate the contribution of environmental factors in human lung cancer occurring in non-smokers.

scholarly journals Anti-human lung cancer activities and survey of gluthation reductase and gluthation S transferase inhibition properties with molecular modeling studies of 2′-Hydroxy-5′-methyl-3′-nitroacetophenone: A pre-clinical trial study

2021 ◽  
Author(s):  
Yawei Dou ◽  
shanshan Lv ◽  
Attalla F. El-kott ◽  
Ayman E. El-kenawy
Keyword(s):  
Lung Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Human Lung ◽  
Antioxidant Properties ◽  
Human Lung Cancer ◽  
Lung Cancers ◽  
Anticancer Properties ◽  
Ic50 Values ◽  
Human Lung Carcinoma

IntroductionRecently, scientists have tried to increase organic chemistry productions for the treatment of many cancers such as lung cancers. In this regard, antioxidant molecules have a special place in the treatment of several cancers. The molecular docking method was found to calculate the biological activity of the 2′-Hydroxy-5′-methyl-3′-nitroacetophenone (2′-H-5′-M-3′-N) molecule against the enzymes studied.Material and methodsIn these calculations, the enzymes used are gluthation reductase (GR) enzyme and Glutathione S-Transferase (GT) enzyme, respectively. After the modeling calculations were completed, the ADME/T parameters were examined to calculate the future drug use properties of the 2′-H-5′-M-3′-N molecule. To survey the antioxidant properties of 2′-H-5′-M-3′-N, the DPPH test was used. Several human lung adenocarcinoma cell lines i.e., lung moderately differentiated adenocarcinoma (LC-2/ad), lung poorly differentiated adenocarcinoma (PC-14), and lung well-differentiated bronchogenic adenocarcinoma (HLC-1) cell lines were used to determine the anticancer properties of the recent molecule.ResultsCell viability of 2′-H-5′-M-3′-N was very low against PC-14, LC-2/ad, and HLC-1 cell lines without any cytotoxicity on the normal cell line. The IC50 values of 2′-H-5′-M-3′-N against LC-2/ad, PC-14, and HLC-1 cell lines were found 475, 250, and 691 µg/mL, respectively. The best anti-human lung cancer properties of 2′-H-5′-M-3′-N against the above cell lines was in the case of PC-14 cell line.ConclusionsAs mentioned, the 2′-H-5′-M-3′-N had significant antioxidant and anti-human lung cancer properties. It appears that the anti-human lung carcinoma effect of 2′-H-5′-M-3′-N is due to their antioxidant effects.

scholarly journals Epigenetic Silencing of TMEM176A Activates ERK Signaling in Human Lung Cancer

2020 ◽  
pp. 1-11
Author(s):  
Liming Hu ◽  
Fuyou Zhou ◽  
Hongxia Li ◽  
James G Herman ◽  
Liming Hu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Promoter Region ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Erk Signaling ◽  
Human Lung Cancer ◽  
Lung Cancers ◽  
H460 Cells ◽  
Partially Methylated

Background: The function of TMEM176A in human lung cancer remains to be elucidated. Materials & Methods: Nine cell lines and 123 cases of lung cancers were employed. Results: TMEM176A was highly expressed in H727 cells, reduced expression was observed in A549, H446 and H460 cells, loss of expression was found in H157, H1563, H358, H1299 and H23 cells. TMEM176A was unmethylated in H727 cells, partially methylated in A549, H446 and H460 cells, and fully methylated in H157, H1563, H358, H1299 and H23 cells. Loss of/reduced expression of TMEM176A is correlated to promoter region methylation. Restoration of TMEM176A expression was induced by 5-AZA-2- deoxycytidine in complete methylated cells, increased expression of TMEM176A was observed in partially methylated cells. These results suggest that TMEM176A is regulated by promoter region methylation in lung cancer cells. TMEM176A was methylated in 53.66% (66/123) of non-small cell lung cancers (NSCLCs) samples. Reduced expression of TMEM176A was associated with promoter region methylation in 40 cases of matched primary NSCLCs and adjacent tissue samples (P<0.05). TMEM176A expression induced cell apoptosis, inhibited colony formation, cell proliferation, migration and invasion. Conclusion: Methylation of TMEM176A activated ERK signaling in lung cancer cells. TMEM176A suppressed human lung cancer cell xenograft growth in mice.

scholarly journals Polo-like kinase 4 inhibition produces polyploidy and apoptotic death of lung cancers

2018 ◽  
Vol 115 (8) ◽  
pp. 1913-1918 ◽  
Author(s):  
Masanori Kawakami ◽  
Lisa Maria Mustachio ◽  
Lin Zheng ◽  
Yulong Chen ◽  
Jaime Rodriguez-Canales ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Dna Content ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Normal Lung ◽  
Lung Cancers ◽  
Centriole Duplication ◽  
Apoptotic Death

Polo-like kinase 4 (PLK4) is a serine/threonine kinase regulating centriole duplication. CFI-400945 is a highly selective PLK4 inhibitor that deregulates centriole duplication, causing mitotic defects and death of aneuploid cancers. Prior work was substantially extended by showing CFI-400945 causes polyploidy, growth inhibition, and apoptotic death of murine and human lung cancer cells, despite expression of mutated KRAS or p53. Analysis of DNA content by propidium iodide (PI) staining revealed cells with >4N DNA content (polyploidy) markedly increased after CFI-400945 treatment. Centrosome numbers and mitotic spindles were scored. CFI-400945 treatment produced supernumerary centrosomes and mitotic defects in lung cancer cells. In vivo antineoplastic activity of CFI-400945 was established in mice with syngeneic lung cancer xenografts. Lung tumor growth was significantly inhibited at well-tolerated dosages. Phosphohistone H3 staining of resected lung cancers following CFI-400945 treatment confirmed the presence of aberrant mitosis. PLK4 expression profiles in human lung cancers were explored using The Cancer Genome Atlas (TCGA) and RNA in situ hybridization (RNA ISH) of microarrays containing normal and malignant lung tissues. PLK4 expression was significantly higher in the malignant versus normal lung and conferred an unfavorable survival (P < 0.05). Intriguingly, cyclin dependent kinase 2 (CDK2) antagonism cooperated with PLK4 inhibition. Taken together, PLK4 inhibition alone or as part of a combination regimen is a promising way to combat lung cancer.

scholarly journals S-phase kinase-associated protein 2 positively controls mitotic arrest deficient 2 in lung cancer cells

2016 ◽  
Author(s):  
Tonghai Huang ◽  
Lin Yang ◽  
Guangsuo Wang ◽  
Guanggui Ding ◽  
Bin Peng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Spindle Assembly Checkpoint ◽  
Human Lung ◽  
Mitotic Arrest ◽  
S Phase ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Lung Cancers ◽  
Protein Levels

Background. Mitotic arrest deficient 2 (Mad2) is a key component of spindle assembly checkpoint and overexpressed in human lung cancers, but the mechanism of the deregulation of Mad2 in lung cancer is largely unknown. We aim to investigate the regulation of Mad2 by S-phase kinase-associated protein 2 (Skp2) in human lung cancer cells. Methods. Human lung cancer A549 and NCI-H1975 cells were transfected with MAD2 and SKP2 siRNAs or plasmids to silence or overexpress MAD2 and SKP2. Flavopiridol and HLM006474 were used to inhibit cyclin dependent kinases (CDKs) and E2F1, respectively. mRNA and protein levels were determined by real-time PCR and Western blot, respectively. Cell cycle progression was assayed by flow cytometery. Results. Knockdown of Skp2 by siRNA decreased Mad2 mRNA and protein levels in A549 and NCI-H1299 cells, accompanied with upregulation of p27 but decrease of the phosphorylation of retinoblastoma (Rb). In contrast, ectopic overexpression of Skp2 increased Mad2 mRNA and protein levels and phosphorylation of Rb, while decreased p27. Pharmacological inhibition of CDK1/2 by flavopiridol or E2F1 with HLM006474 led to downregulation of Mad2 expression, and prevented the increase of Mad2 expression by Skp2. Accordingly, silencing of either Mad2 or Skp2 impaired the mitosis arrest in response to nocadazole. Conclusion. SKP2 positively regulates the gene expression of MAD2 through p27-CDKs-E2F1 signaling pathway, suggesting that deregulation of Skp2 may lead to upregulation of Mad2 via enhancing the activity of CDKs in human lung cancers. Our findings may provide an explanation of the simultaneous upregulation of MAD2 and SKP2 in lung cancer and potential targets for the development of molecular targeted therapy for lung cancers.

scholarly journals S-phase kinase-associated protein 2 positively controls mitotic arrest deficient 2 in lung cancer cells

2016 ◽  
Author(s):  
Tonghai Huang ◽  
Lin Yang ◽  
Guangsuo Wang ◽  
Guanggui Ding ◽  
Bin Peng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Spindle Assembly Checkpoint ◽  
Human Lung ◽  
Mitotic Arrest ◽  
S Phase ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Lung Cancers ◽  
Protein Levels

Background. Mitotic arrest deficient 2 (Mad2) is a key component of spindle assembly checkpoint and overexpressed in human lung cancers, but the mechanism of the deregulation of Mad2 in lung cancer is largely unknown. We aim to investigate the regulation of Mad2 by S-phase kinase-associated protein 2 (Skp2) in human lung cancer cells. Methods. Human lung cancer A549 and NCI-H1975 cells were transfected with MAD2 and SKP2 siRNAs or plasmids to silence or overexpress MAD2 and SKP2. Flavopiridol and HLM006474 were used to inhibit cyclin dependent kinases (CDKs) and E2F1, respectively. mRNA and protein levels were determined by real-time PCR and Western blot, respectively. Cell cycle progression was assayed by flow cytometery. Results. Knockdown of Skp2 by siRNA decreased Mad2 mRNA and protein levels in A549 and NCI-H1299 cells, accompanied with upregulation of p27 but decrease of the phosphorylation of retinoblastoma (Rb). In contrast, ectopic overexpression of Skp2 increased Mad2 mRNA and protein levels and phosphorylation of Rb, while decreased p27. Pharmacological inhibition of CDK1/2 by flavopiridol or E2F1 with HLM006474 led to downregulation of Mad2 expression, and prevented the increase of Mad2 expression by Skp2. Accordingly, silencing of either Mad2 or Skp2 impaired the mitosis arrest in response to nocadazole. Conclusion. SKP2 positively regulates the gene expression of MAD2 through p27-CDKs-E2F1 signaling pathway, suggesting that deregulation of Skp2 may lead to upregulation of Mad2 via enhancing the activity of CDKs in human lung cancers. Our findings may provide an explanation of the simultaneous upregulation of MAD2 and SKP2 in lung cancer and potential targets for the development of molecular targeted therapy for lung cancers.

Ras Denitrosylation in Human Lung Cancer

2012 ◽  
Vol 3 (2) ◽  
pp. 135-139
Author(s):  
Benjamin Gaston ◽  
Nadzeya Marozkina
Keyword(s):  
Lung Cancer ◽  
Human Lung ◽  
Human Lung Cancer

MicroRNAs expression signature in human lung cancer cell

2014 ◽  
Author(s):  
Geyu Liang ◽  
Xikai Wang ◽  
Yanqiu Zhang ◽  
Yanyun Fu ◽  
Lihong Yin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cell ◽  
Human Lung ◽  
Human Lung Cancer ◽  
Lung Cancer Cell ◽  
Human Lung Cancer Cell ◽  
Expression Signature
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