scholarly journals Jaagsiekte sheep retrovirus infection induces changes in microRNA expression in the ovine lung

2021 ◽  
Author(s):  
Maria Contreras Garcia ◽  
Anna Eleonora Karagianni ◽  
Deepali Vasoya ◽  
Siddharth Jayaraman ◽  
Yao-Tang Lin ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Small Rna ◽  
Mirna Expression ◽  
Human Lung ◽  
Alveolar Epithelial Cells ◽  
Human Lung Cancer ◽  
Small Rna Sequencing ◽  
Large Animal ◽  
Jaagsiekte Sheep Retrovirus ◽  
Human Lung Adenocarcinoma

Ovine pulmonary adenocarcinoma (OPA) is an infectious neoplastic lung disease of sheep caused by jaagsiekte sheep retrovirus. OPA is an important veterinary problem and is also a valuable large animal model for human lung adenocarcinoma. JSRV infects type 2 alveolar epithelial cells in the lung and induces the growth of tumors, but little is known about the molecular events that lead to the activation of oncogenic pathways in infected cells. MicroRNAs (miRNAs) are small RNA molecules of approximately 22 nucleotides with important roles in regulating gene expression in eukaryotes and with well-established roles in cancer. Here we used small-RNA sequencing to investigate the changes in miRNA expression that occur in JSRV-infected ovine lung. After filtering out low abundance miRNAs, we identified expression of 405 miRNAs, 32 of which were differentially expressed in JSRV-infected lung compared to mock-inoculated control lung. Highly upregulated miRNAs included miR-182, miR-183, miR-96 and miR-135b, which have also been associated with oncogenic changes in human lung cancer. Network analysis of genes potentially targeted by the deregulated miRNAs identified their involvement in pathways known to be dysregulated in OPA. We found no evidence to support the existence of miRNAs encoded by JSRV. This study provides the first information on miRNA expression in OPA and identifies a number of targets for future studies into the role of these molecules in the pathogenesis of this unique veterinary model for human lung adenocarcinoma.

scholarly journals Transcriptional Response of Ovine Lung to Infection with Jaagsiekte Sheep Retrovirus

2019 ◽  
Vol 93 (21) ◽  
Author(s):  
Anna Eleonora Karagianni ◽  
Deepali Vasoya ◽  
Jeanie Finlayson ◽  
Henny M. Martineau ◽  
Ann R. Wood ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Animal Model ◽  
Lung Adenocarcinoma ◽  
Human Lung ◽  
Transcriptional Response ◽  
Human Lung Cancer ◽  
Ovine Pulmonary Adenocarcinoma ◽  
Jaagsiekte Sheep Retrovirus ◽  
Human Lung Adenocarcinoma ◽  
Naturally Occurring

ABSTRACT Jaagsiekte sheep retrovirus (JSRV) is the etiologic agent of ovine pulmonary adenocarcinoma (OPA), a neoplastic lung disease of sheep. OPA is an important economic and welfare issue for sheep farmers and a valuable naturally occurring animal model for human lung adenocarcinoma. Here, we used RNA sequencing to study the transcriptional response of ovine lung tissue to infection by JSRV. We identified 1,971 ovine genes differentially expressed in JSRV-infected lung compared to noninfected lung, including many genes with roles in carcinogenesis and immunomodulation. The differential expression of selected genes was confirmed using immunohistochemistry and reverse transcription-quantitative PCR. A key finding was the activation of anterior gradient 2, yes-associated protein 1, and amphiregulin in OPA tumor cells, indicating a role for this oncogenic pathway in OPA. In addition, there was differential expression of genes related to innate immunity, including genes encoding cytokines, chemokines, and complement system proteins. In contrast, there was little evidence for the upregulation of genes involved in T-cell immunity. Many genes related to macrophage function were also differentially expressed, reflecting the increased abundance of these cells in OPA-affected lung tissue. Comparison of the genes differentially regulated in OPA with the transcriptional changes occurring in human lung cancer revealed important similarities and differences between OPA and human lung adenocarcinoma. This study provides valuable new information on the pathogenesis of OPA and strengthens the use of this naturally occurring animal model for human lung adenocarcinoma. IMPORTANCE Ovine pulmonary adenocarcinoma is a chronic respiratory disease of sheep caused by jaagsiekte sheep retrovirus (JSRV). OPA is a significant economic problem for sheep farmers in many countries and is a valuable animal model for some forms of human lung cancer. Here, we examined the changes in host gene expression that occur in the lung in response to JSRV infection. We identified a large number of genes with altered expression in infected lung, including factors with roles in cancer and immune system function. We also compared the data from OPA to previously published data from human lung adenocarcinoma and found a large degree of overlap in the genes that were dysregulated. The results of this study provide exciting new avenues for future studies of OPA and may have comparative relevance for understanding human lung cancer.

The ADAM17 protease promotes tobacco smoke carcinogen-induced lung tumorigenesis

2019 ◽  
Vol 41 (4) ◽  
pp. 527-538 ◽  
Author(s):  
Mohamed I Saad ◽  
Louise McLeod ◽  
Liang Yu ◽  
Hiromichi Ebi ◽  
Saleela Ruwanpura ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Tobacco Smoke ◽  
Human Lung ◽  
Human Lung Cancer ◽  
Smoking History ◽  
Lung Carcinogenesis ◽  
Wild Type Littermate ◽  
Human Lung Adenocarcinoma ◽  
Erk Mapk

Abstract Lung cancer is the leading cause of cancer-related mortality, with most cases attributed to tobacco smoking, in which nicotine-derived nitrosamine ketone (NNK) is the most potent lung carcinogen. The ADAM17 protease is responsible for the ectodomain shedding of many pro-tumorigenic cytokines, growth factors and receptors, and therefore is an attractive target in cancer. However, the role of ADAM17 in promoting tobacco smoke carcinogen-induced lung carcinogenesis is unknown. The hypomorphic Adam17ex/ex mice—characterized by reduced global ADAM17 expression—were backcrossed onto the NNK-sensitive pseudo-A/J background. CRISPR-driven and inhibitor-based (GW280264X, and ADAM17 prodomain) ADAM17 targeting was employed in the human lung adenocarcinoma cell lines A549 and NCI-H23. Human lung cancer biopsies were also used for analyses. The Adam17ex/ex mice displayed marked protection against NNK-induced lung adenocarcinoma. Specifically, the number and size of lung lesions in NNK-treated pseudo-A/J Adam17ex/ex mice were significantly reduced compared with wild-type littermate controls. This was associated with lower proliferative index throughout the lung epithelium. ADAM17 targeting in A549 and NCI-H23 cells led to reduced proliferative and colony-forming capacities. Notably, among select ADAM17 substrates, ADAM17 deficiency abrogated shedding of the soluble IL-6 receptor (sIL-6R), which coincided with the blockade of sIL-6R-mediated trans-signaling via ERK MAPK cascade. Furthermore, NNK upregulated phosphorylation of p38 MAPK, whose pharmacological inhibition suppressed ADAM17 threonine phosphorylation. Importantly, ADAM17 threonine phosphorylation was significantly upregulated in human lung adenocarcinoma with smoking history compared with their cancer-free controls. Our study identifies the ADAM17/sIL-6R/ERK MAPK axis as a candidate therapeutic strategy against tobacco smoke-associated lung carcinogenesis.

scholarly journals Fabrication of Ag nanoparticles mediated by extract of plant and determination of the ‎anti-human lung cancer effects

2021 ◽  
Author(s):  
Hongjiang Yan ◽  
Ruoxuan Xu ◽  
Yanmei Song ◽  
Weinian Gao ◽  
Helin Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cell Lines ◽  
Aqueous Extract ◽  
Ag Nanoparticles ◽  
Human Lung ◽  
Human Lung Cancer ◽  
Ag Nps ◽  
Human Lung Adenocarcinoma ◽  
Vis Spectroscopy ◽  
Thymus Capitatus

IntroductionThe present work demonstrates the synthesis of Ag nanoparticles (Ag NPs) by aqueous extract of Thymus ‎capitatus as green reductant and capping agent without any toxic reagent. ‎Material and methodsPhysicochemical characteristics of the said nanocomposite were elucidated by field emission scanning electron ‎microscopy (FE-SEM), fourier-transform infrared spectroscopy (FTIR), and UV-Vis Spectroscopy. ‎ResultsThe biogenic Ag NPs are uniformly globular. The Ag NPs has been explored biologically in the anticancer and ‎antioxidant assays. In the cellular and molecular part of the recent study, the treated cells with Ag NPs were ‎assessed by MTT assay for 48h about the cytotoxicity and anti-human lung adenocarcinoma properties on ‎normal (HUVEC) and lung adenocarcinoma cell lines i.e. lung well-differentiated bronchogenic adenocarcinoma ‎‎(HLC-1), lung moderately differentiated adenocarcinoma (LC-2/ad), and lung poorly differentiated ‎adenocarcinoma (PC-14). The viability of malignant lung cell line reduced dose-dependently in the presence of ‎Ag NPs. The IC50 of Ag NPs were 209, 185, and 106 µg/mL against HLC-1, LC-2/ad, and PC-14 cell lines, ‎respectively. In the antioxidant test, the IC50 of Ag NPs and BHT against DPPH free radicals were 86 and 76 ‎‎µg/mL, respectively. ‎ConclusionsAfter clinical study, Ag NPs containing Thymus capitatus leaf aqueous extract may be used to formulate a new ‎chemotherapeutic drug or supplement to treat the several types of human lung adenocarcinoma. ‎

FOX-A1 Contributes to Acquisition of Chemoresistance in Human Lung Adenocarcinoma via Transactivation of SOX5

2019 ◽  
Author(s):  
Dongqin Chen ◽  
Rui Wang ◽  
Chen Yu ◽  
Fei Cao ◽  
Xuefeng Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Human Lung ◽  
Human Lung Adenocarcinoma

Isoorientin Decreases Cell Migration via Decreasing Functional Activity and Molecular Expression of Proton-Linked Monocarboxylate Transporters in Human Lung Cancer Cells

2020 ◽  
Vol 48 (01) ◽  
pp. 201-222
Author(s):  
Hsu-Kai Huang ◽  
Shin-Yi Lee ◽  
Shu-Fen Huang ◽  
Yu-San Lin ◽  
Shih-Chi Chao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Migration ◽  
Lung Adenocarcinoma ◽  
Cell Viability ◽  
Cancer Cells ◽  
Functional Activity ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Human Lung Cancer Cells

Aggressive tumor cells mainly rely on glycolysis, and further release vast amounts of lactate and protons by monocarboxylate transporter (MCT), which causes a higher intracellular pH (pHi) and acidic extracellular pH. Isoorientin, a principle flavonoid compound extracted from several plant species, shows various pharmacological activities. However, effects of isoorientin on anticancer and MCT await to explore in human lung cancer cells. Human lung cancer tissues were obtained from cancer patients undergoing surgery, while the human lung adenocarcinoma cells (A549) were bought commercially. Change of pHi was detected by microspectrofluorometry method with a pH-sensitive fluorescent dye, BCECF. MTT and wound-healing assay were used to detect the cell viability and migration, respectively. Western blot techniques and immunocytochemistry staining were used to detect the protein expression. Our results indicated that the expression of MCTs1/4 and CD147 were upregulated significantly in human lung tissues. In experiments of A549 cells, under HEPES-buffer, the resting pHi was 7.47, and isoorientin (1–300[Formula: see text][Formula: see text]M) inhibited functional activity of MCT concentration-dependently (up to [Formula: see text]%). Pretreatment with isoorientin (3–100[Formula: see text][Formula: see text]M) for 24[Formula: see text]h, MCT activity and cell migration were significantly inhibited ([Formula: see text]% and [Formula: see text]%, respectively), while the cell viability was not affected. Moreover, the expression of MCTs1/4, CD147, and matrix metalloproteinase (MMP) 2/9 were significantly down regulated. In summary, MCTs1/4 and CD147 are significantly upregulated in human lung adenocarcinoma tissues, and isoorientin inhibits cells-migration by inhibiting activity/expression of MCTs1/4 and MMPs2/9 in human lung cancer cells. These novel findings suggest that isoorientin could be a promising pharmacological agent for lung cancer.

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