scholarly journals RETRACTED ARTICLE: Oncogenic transformation of human lung bronchial epithelial cells induced by arsenic involves ROS-dependent activation of STAT3-miR-21-PDCD4 mechanism

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Poyil Pratheeshkumar ◽  
Young-Ok Son ◽  
Sasidharan Padmaja Divya ◽  
Lei Wang ◽  
Zhuo Zhang ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Cell Transformation ◽  
Arsenic Exposure ◽  
Malignant Cell ◽  
Bronchial Epithelial ◽  
Signaling Axis ◽  
Retracted Article ◽  
Programmed Cell Death 4 ◽  
Malignant Cell Transformation

Abstract Arsenic is a well-documented human carcinogen. The present study explored the role of the onco-miR, miR-21 and its target protein, programmed cell death 4 (PDCD4) in arsenic induced malignant cell transformation and tumorigenesis. Our results showed that treatment of human bronchial epithelial (BEAS-2B) cells with arsenic induces ROS through p47phox, one of the NOX subunits that is the key source of arsenic-induced ROS. Arsenic exposure induced an upregulation of miR-21 expression associated with inhibition of PDCD4, and caused malignant cell transformation and tumorigenesis of BEAS-2B cells. Indispensably, STAT3 transcriptional activation by IL-6 is crucial for the arsenic induced miR-21 increase. Upregulated miR-21 levels and suppressed PDCD4 expression was also observed in xenograft tumors generated with chronic arsenic exposed BEAS-2B cells. Stable shut down of miR-21, p47phox or STAT3 and overexpression of PDCD4 or catalase in BEAS-2B cells markedly inhibited the arsenic induced malignant transformation and tumorigenesis. Similarly, silencing of miR-21 or STAT3 and forced expression of PDCD4 in arsenic transformed cells (AsT) also inhibited cell proliferation and tumorigenesis. Furthermore, arsenic suppressed the downstream protein E-cadherin expression and induced β-catenin/TCF-dependent transcription of uPAR and c-Myc. These results indicate that the ROS-STAT3-miR-21-PDCD4 signaling axis plays an important role in arsenic -induced carcinogenesis.

scholarly journals MicroRNA profiling in BEAS-2B cells exposed to alpha radiation reveals potential biomarkers for malignant cellular transformation

2020 ◽  
Vol 9 (6) ◽  
pp. 834-844
Author(s):  
Xuhong Dang ◽  
Haipeng Lin ◽  
Youchen Li ◽  
Xiuli Guo ◽  
Yayi Yuan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epithelial Cells ◽  
Alpha Particle ◽  
Cell Transformation ◽  
Malignant Cell ◽  
Bronchial Epithelial Cells ◽  
Bronchial Epithelial ◽  
Radon Exposure ◽  
Particle Irradiation ◽  
Malignant Cell Transformation

Abstract The carcinogenicity of radon has been convincingly documented through epidemiological studies of underground miners. The risk of lung cancer from radon exposure is due to the continuous radioactive decay of this gas and subsequent emission of high-energy alpha decay particles. And the bronchial epithelial cells are the main targets of radon exposure. However, there is a lack of early warning indicators of lung cancer caused by radon in the physical examination of populations involved in occupations with higher exposure to radon. To assess the potential of a molecular-based marker approach for the early detection of human lung cancer induced by radon, human bronchial epithelial cell injury models induced by alpha-particle irradiation were constructed. The results of transwell migration assay, transwell invasion assay, and the expression of the epithelial–mesenchymal transition-related proteins showed that malignant cell transformation could be triggered by alpha irradiation. Potential microRNAs (miRNAs) (hsa-miR-3907, hsa-miR-6732-3p, hsa-miR-4788, hsa-miR-5001-5p, and hsa-miR-4257) were screened using miRNA chips in cell models. The pathway analyses of miRNAs selected using DIANA-miRPath v3.0 showed that miRNAs involved in malignant cell transformation were associated with cell adhesion molecules, extracellular matrix receptor interaction, and proteoglycans in cancer, among others, which are closely related to the occurrence and development of carcinogenesis. Reverse Transcription Quantitative Real-Time PCR (RT-qPCR) assay showed that five screened miRNAs were up-regulated in five lung cancer tissue samples. In conclusion, the results indicated that hsa-miR-3907, hsa-miR-6732-3p, hsa-miR-4788, hsa-miR-5001-5p, and hsa-miR-4257 may be potential early markers of the malignant transformation of bronchial epithelial cells induced by alpha-particle irradiation.

Hodgkin Lymphoma

2018 ◽  
Author(s):  
Henrik Hjalgrim ◽  
Mads Melbye ◽  
Pagona Lagiou
Keyword(s):  
Natural History ◽  
Hodgkin Lymphoma ◽  
Cell Transformation ◽  
Malignant Cell ◽  
Future Research ◽  
Barr Virus ◽  
History Of ◽  
Epstein Barr ◽  
Malignant Cell Transformation

The descriptive epidemiology of Hodgkin lymphoma (HL) has demonstrated marked variation by age, sex, social class, and time, strongly suggesting both a role of environmental factors and the existence of etiologically diverse HL subtypes. There is increasing evidence that Epstein Barr virus (EBV)–positive and EBV-negative classical HLs define two variants with separate etiologies. The risk for both increases with family history, whereas immune dysfunction and infectious mononucleosis have been implicated in EBV-positive HL risk only. Despite being the less common of the two, the natural history of EBV-positive HL is currently the best understood, both with respect to how EBV may contribute to malignant cell transformation and in relation to constitutional and environmental risk factors. Meanwhile, the understanding of the natural history of EBV-negative HL is meager. Future research for EBV-negative HL is expected to focus on its presumed infectious etiology, for which there are currently no strong candidates.

scholarly journals The Role of the MCTS1 and DENR Proteins in Regulating the Mechanisms Associated with Malignant Cell Transformation

Acta Naturae ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 98-105
Author(s):  
Elena Yu. Shyrokova ◽  
Vladimir S. Prassolov ◽  
Pavel V. Spirin
Keyword(s):  
Signaling Pathways ◽  
Target Genes ◽  
Cell Transformation ◽  
Malignant Cell ◽  
Tumor Formation ◽  
Anti Cancer ◽  
Differentiation And Proliferation ◽  
Mutant Genes ◽  
Malignant Cell Transformation

The mutations associated with malignant cell transformation are believed to disrupt the expression of a significant number of normal, non-mutant genes. The proteins encoded by these genes are involved in the regulation of many signaling pathways that are responsible for differentiation and proliferation, as well as sensitivity to apoptotic signals, growth factors, and cytokines. Abnormalities in the balance of signaling pathways can lead to the transformation of a normal cell, which results in tumor formation. Detection of the target genes and the proteins they encode and that are involved in the malignant transformation is one of the major evolutions in anti-cancer biomedicine. Currently, there is an accumulation of data that shed light on the role of the MCTS1 and DENR proteins in oncogenesis.

scholarly journals Synthesis and in vitro characterization of the genotoxic, mutagenic and cell-transforming potential of nitrosylated heme

2020 ◽  
Vol 94 (11) ◽  
pp. 3911-3927 ◽  
Author(s):  
Tina Kostka ◽  
Jörg Fohrer ◽  
Claudia Guigas ◽  
Karlis Briviba ◽  
Nina Seiwert ◽  
...  
Keyword(s):  
Cell Transformation ◽  
Malignant Cell ◽  
Red Meat ◽  
Colorectal Carcinogenesis ◽  
In Vivo Studies ◽  
Processed Meat ◽  
Cell Transforming ◽  
Malignant Cell Transformation

Abstract Data from epidemiological studies suggest that consumption of red and processed meat is a factor contributing to colorectal carcinogenesis. Red meat contains high amounts of heme, which in turn can be converted to its nitrosylated form, NO-heme, when adding nitrite-containing curing salt to meat. NO-heme might contribute to colorectal cancer formation by causing gene mutations and could thereby be responsible for the association of (processed) red meat consumption with intestinal cancer. Up to now, neither in vitro nor in vivo studies characterizing the mutagenic and cell transforming potential of NO-heme have been published due to the fact that the pure compound is not readily available. Therefore, in the present study, an already existing synthesis protocol was modified to yield, for the first time, purified NO-heme. Thereafter, newly synthesized NO-heme was chemically characterized and used in various in vitro approaches at dietary concentrations to determine whether it can lead to DNA damage and malignant cell transformation. While NO-heme led to a significant dose-dependent increase in the number of DNA strand breaks in the comet assay and was mutagenic in the HPRT assay, this compound tested negative in the Ames test and failed to induce malignant cell transformation in the BALB/c 3T3 cell transformation assay. Interestingly, the non-nitrosylated heme control showed similar effects, but was additionally able to induce malignant transformation in BALB/c 3T3 murine fibroblasts. Taken together, these results suggest that it is the heme molecule rather than the NO moiety which is involved in driving red meat-associated carcinogenesis.

JAK2/STAT3 in role of arsenic-induced cell proliferation: a systematic review and meta-analysis

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Shugang Li ◽  
Shanshan Ran ◽  
Qingxin Ren
Keyword(s):  
Cell Proliferation ◽  
Meta Analysis ◽  
Arsenic Concentration ◽  
Arsenic Exposure ◽  
Malignant Cell ◽  
Dose Effect ◽  
Expression Level ◽  
Exposure Concentration ◽  
Effect Relationship

Abstract Objectives Malignant cell proliferation is one of the important mechanisms of arsenic poisoning. A large number of studies have shown that STAT3 plays an important role in cell malignant proliferation, but there are still many contradictions in the effect of arsenic on JAK2/STAT3. This study aims to explore the role of JAK2/STAT3 in arsenic-induced cell proliferation. Methods By taking normal cells as the research object and using Standard Mean Difference (SMD) as the effect size, meta-analysis was used to explore the effect of arsenic on JAK2/STAT3. Then, the dose-effect Meta was used to further clarify the dose-effect relationship of arsenic on JAK2/STAT3. Results Through meta-analysis, this study found that arsenic could promote the phosphorylation of STAT3 (SMD=4.21, 95%CI [1.05, 7.37]), and increase IL-6 and p-JAK2, Vimentin, VEGF expression levels, thereby inducing malignant cell proliferation. In addition, this study also found that arsenic exposure dose (<5 μmol m−3), time(<24 h) and cell type were important sources of heterogeneity in the process of exploring the effects of arsenic on p-STAT3, IL-6 and p-JAK2. Dose-effect relationship meta-analysis results showed that arsenic exposure significantly increased the expression level of IL-6. When the arsenic exposure concentration was less than 7 μmol m−3, the expression level of p-JAK2 upregulated significantly as the arsenic exposure concentration gradually increasing. Moreover, the expression level of p-STAT3 elevated significantly with the gradual increase of the arsenic concentration under 5 μmol m−3 of arsenic exposure, but the expression level of p-STAT3 gradually decreases when the concentration is greater than 5 μmol m−3. Conclusions Exposure to low dose of arsenic could promote the expression of JAK2/STAT3 and induce the malignant proliferation of cells through upregulating IL-6, and there was dose-effect relationship among them.

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