The Effect of NNK, A Tobacco Smoke Carcinogen, on the miRNA and Mismatch DNA Repair Expression Profiles in Lung and Head and Neck Squamous Cancer Cells

Tobacco smoking is a common risk factor for lung cancer and head and neck cancer. Molecular changes such as deregulation of miRNA expression have been linked to tobacco smoking in both types of cancer. Dysfunction of the Mismatch DNA repair (MMR) mechanism has also been associated with a poor prognosis of these cancers, while a cross-talk between specific miRNAs and MMR genes has been previously proposed. We hypothesized that exposure of lung and head and neck squamous cancer cells (NCI and FaDu, respectively) to tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is capable of altering the expression of MSH2 and MLH1, key MMR components, by promoting specific miRNA deregulation. We found that either a low (1 μM) or high (2 μM) dose of NNK induced significant upregulation of “oncomirs” miR-21 and miR-155 and downregulation of “tumor suppressor” miR-422a, as well as the reduction of MMR protein and mRNA expression, in NCI and FaDu, compared to controls. Inhibition of miR-21 restored the NNK-induced reduced MSH2 phenotype in both NCI and FaDu, indicating that miR-21 might contribute to MSH2 regulation. Finally, NNK exposure increased NCI and FaDu survival, promoting cancer cell progression. We provide novel findings that deregulated miR-21, miR-155, and miR-422a and MMR gene expression patterns may be valuable biomarkers for lung and head and neck squamous cell cancer progression in smokers.

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Gene Expression and Transcriptome Profiling of Changes in a Cancer Cell Line Post-Exposure to Cadmium Telluride Quantum Dots: Possible Implications in Oncogenesis

Dose-Response ◽

10.1177/15593258211019880 ◽

2021 ◽

Vol 19 (2) ◽

pp. 155932582110198

Author(s):

Mohammed S. Aldughaim ◽

Mashael R. Al-Anazi ◽

Marie Fe F. Bohol ◽

Dilek Colak ◽

Hani Alothaid ◽

...

Keyword(s):

Gene Expression ◽

Quantum Dots ◽

Cancer Cells ◽

Cadmium Telluride ◽

Cancer Progression ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Dependent Manner ◽

Cdte Qds ◽

Cadmium Telluride Quantum Dots

Cadmium telluride quantum dots (CdTe-QDs) are acquiring great interest in terms of their applications in biomedical sciences. Despite earlier sporadic studies on possible oncogenic roles and anticancer properties of CdTe-QDs, there is limited information regarding the oncogenic potential of CdTe-QDs in cancer progression. Here, we investigated the oncogenic effects of CdTe-QDs on the gene expression profiles of Chang cancer cells. Chang cancer cells were treated with 2 different doses of CdTe-QDs (10 and 25 μg/ml) at different time intervals (6, 12, and 24 h). Functional annotations helped identify the gene expression profile in terms of its biological process, canonical pathways, and gene interaction networks activated. It was found that the gene expression profiles varied in a time and dose-dependent manner. Validation of transcriptional changes of several genes through quantitative PCR showed that several genes upregulated by CdTe-QD exposure were somewhat linked with oncogenesis. CdTe-QD-triggered functional pathways that appear to associate with gene expression, cell proliferation, migration, adhesion, cell-cycle progression, signal transduction, and metabolism. Overall, CdTe-QD exposure led to changes in the gene expression profiles of the Chang cancer cells, highlighting that this nanoparticle can further drive oncogenesis and cancer progression, a finding that indicates the merit of immediate in vivo investigation.

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Phylogenetic Comparison and Splicing Analysis of the U1 snRNP-specific Protein U1C in Eukaryotes

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.696319 ◽

2021 ◽

Vol 8 ◽

Author(s):

Kai-Lu Zhang ◽

Jian-Li Zhou ◽

Jing-Fang Yang ◽

Yu-Zhen Zhao ◽

Debatosh Das ◽

...

Keyword(s):

Gene Family ◽

Cancer Progression ◽

Expression Profiles ◽

Expression Patterns ◽

Specific Protein ◽

Comprehensive Overview ◽

Small Nuclear Ribonucleoprotein ◽

U1 Snrnp ◽

Multiple Copies ◽

And Function

As a pivotal regulator of 5’ splice site recognition, U1 small nuclear ribonucleoprotein (U1 snRNP)-specific protein C (U1C) regulates pre-mRNA splicing by interacting with other components of the U1 snRNP complex. Previous studies have shown that U1 snRNP and its components are linked to a variety of diseases, including cancer. However, the phylogenetic relationships and expression profiles of U1C have not been studied systematically. To this end, we identified a total of 110 animal U1C genes and compared them to homologues from yeast and plants. Bioinformatics analysis shows that the structure and function of U1C proteins is relatively conserved and is found in multiple copies in a few members of the U1C gene family. Furthermore, the expression patterns reveal that U1Cs have potential roles in cancer progression and human development. In summary, our study presents a comprehensive overview of the animal U1C gene family, which can provide fundamental data and potential cues for further research in deciphering the molecular function of this splicing regulator.

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Targeting UCP2 Suppresses the FAK Signaling and Progression of Human Head and Neck Cancer Cells

Clinical Oncology and Research ◽

10.31487/j.cor.2020.04.09 ◽

2020 ◽

pp. 1-8

Author(s):

Yunfeng Zhao ◽

Cherie Ann Nathan ◽

Chunjing Zhang ◽

Hongyan Du ◽

Manikandan Panchatcharam ◽

...

Keyword(s):

Head And Neck ◽

Cancer Cells ◽

Cancer Progression ◽

Uncoupling Protein ◽

Human Head ◽

Atp Production ◽

Normal Tissues ◽

Tumor Tissues ◽

Lactate Formation

Background: New adjuvant therapies for human head and neck (H&N) cancer to improve the quality of life of the patients are in great demand. Our early studies have demonstrated that uncoupling protein 2 (UCP2) is upregulated in the tumor tissues of H&N cancer compared to the adjacent normal tissues; however, the role of UCP2 in H&N cancer has not been studied. Objective: In this manuscript, we aim to examine whether UCP2 contributes to H&N cancer progression in vitro. Methods: We generated UCP2 stable knockdown H&N cancer cells and detected the effects of UCP2 inhibition on cell proliferation, migration, invasion, 3D spheroid formation, and the sensitivity to a chemodrug treatment. Results: Knockdown of UCP2 suppressed the progression of H&N cancer in vitro, which might be mediated via the following mechanism: 1) increased the G1 phase whereas decreased the S phase of the cell cycle, which could be mediated by suppression of the G1/S regulators including CDK4/6 and cyclin D1. 2) Decreased mitochondrial oxygen consumption, ATP production, and lactate formation, which is consistent with the downregulation of c-Myc. 3) FAK may serve as the upstream signaling molecule, and its action was mediated by Akt and ERK. Conclusions: Our studies first demonstrate that targeting UCP2 may suppress H&N cancer progression in vitro.

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A non-catalytic function of carbonic anhydrase IX contributes to the glycolytic phenotype and pH regulation in human breast cancer cells

Biochemical Journal ◽

10.1042/bcj20190177 ◽

2019 ◽

Vol 476 (10) ◽

pp. 1497-1513 ◽

Cited By ~ 8

Author(s):

Mam Y. Mboge ◽

Zhijuan Chen ◽

Daniel Khokhar ◽

Alyssa Wolff ◽

Lingbao Ai ◽

...

Keyword(s):

Breast Cancer ◽

Carbonic Anhydrase ◽

Cancer Cells ◽

Cancer Progression ◽

Expression Patterns ◽

Extracellular Ph ◽

Carbonic Anhydrase Ix ◽

Monocarboxylate Transporter ◽

Proton Efflux ◽

Ca Ix

AbstractThe most aggressive and invasive tumor cells often reside in hypoxic microenvironments and rely heavily on rapid anaerobic glycolysis for energy production. This switch from oxidative phosphorylation to glycolysis, along with up-regulation of the glucose transport system, significantly increases the release of lactic acid from cells into the tumor microenvironment. Excess lactate and proton excretion exacerbate extracellular acidification to which cancer cells, but not normal cells, adapt. We have hypothesized that carbonic anhydrases (CAs) play a role in stabilizing both intracellular and extracellular pH to favor cancer progression and metastasis. Here, we show that proton efflux (acidification) using the glycolytic rate assay is dependent on both extracellular pH (pHe) and CA IX expression. Yet, isoform-selective sulfonamide-based inhibitors of CA IX did not alter proton flux, which suggests that the catalytic activity of CA IX is not necessary for this regulation. Other investigators have suggested the CA IX co-operates with the MCT transport family to excrete protons. To test this possibility, we examined the expression patterns of selected ion transporters and show that members of this family are differentially expressed within the molecular subtypes of breast cancer. The most aggressive form of breast cancer, triple-negative breast cancer, appears to co-ordinately express the monocarboxylate transporter 4 (MCT4) and carbonic anhydrase IX (CA IX). This supports a possible mechanism that utilizes the intramolecular H+ shuttle system in CA IX to facilitate proton efflux through MCT4.

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Resveratrol causes COX-2- and p53-dependent apoptosis in head and neck squamous cell cancer cells

Journal of Cellular Biochemistry ◽

10.1002/jcb.21772 ◽

2008 ◽

Vol 104 (6) ◽

pp. 2131-2142 ◽

Cited By ~ 48

Author(s):

Hung-Yun Lin ◽

MingZeng Sun ◽

Heng-Yuan Tang ◽

Tessa M. Simone ◽

Yun-Hsuan Wu ◽

...

Keyword(s):

Head And Neck ◽

Cancer Cells ◽

Squamous Cell ◽

Squamous Cell Cancer ◽

Cell Cancer ◽

Cox 2 ◽

Neck Squamous Cell Cancer

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Dexamethasone Inhibits Spheroid Formation of Thyroid Cancer Cells Exposed to Simulated Microgravity

Cells ◽

10.3390/cells9020367 ◽

2020 ◽

Vol 9 (2) ◽

pp. 367 ◽

Cited By ~ 3

Author(s):

Melnik ◽

Sahana ◽

Corydon ◽

Kopp ◽

Nassef ◽

...

Keyword(s):

Thyroid Cancer ◽

Cancer Cells ◽

Cancer Progression ◽

Cancer Biology ◽

Expression Patterns ◽

Three Dimensional ◽

Signal Pathways ◽

Dependent Manner ◽

Spheroid Formation ◽

Mesenchymal Transition

Detachment and the formation of spheroids under microgravity conditions can be observed with various types of intrinsically adherent human cells. In particular, for cancer cells this process mimics metastasis and may provide insights into cancer biology and progression that can be used to identify new drug/target combinations for future therapies. By using the synthetic glucocorticoid dexamethasone (DEX), we were able to suppress spheroid formation in a culture of follicular thyroid cancer (FTC)-133 cells that were exposed to altered gravity conditions on a random positioning machine. DEX inhibited the growth of three-dimensional cell aggregates in a dose-dependent manner. In the first approach, we analyzed the expression of several factors that are known to be involved in key processes of cancer progression such as autocrine signaling, proliferation, epithelial–mesenchymal transition, and anoikis. Wnt/β-catenin signaling and expression patterns of important genes in cancer cell growth and survival, which were further suggested to play a role in three-dimensional aggregation, such as NFKB2, VEGFA, CTGF, CAV1, BCL2(L1), or SNAI1, were clearly affected by DEX. Our data suggest the presence of a more complex regulation network of tumor spheroid formation involving additional signal pathways or individual key players that are also influenced by DEX.

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MicroRNA expression profiles associated with pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.153 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 153-153 ◽

Cited By ~ 2

Author(s):

N. A. Schultz ◽

J. Werner ◽

H. Willenbrock ◽

A. Roslind ◽

T. Horn ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Cells ◽

Tumor Tissue ◽

Expression Profiles ◽

Expression Patterns ◽

Differentially Expressed ◽

Ductal Adenocarcinoma ◽

Mirna Expression Pattern ◽

Quantile Normalisation ◽

Highly Correlated

153 Background: The aim was: 1) to define the global microRNA (miRNA) expression pattern in pancreatic cancer (PC) and compare it with normal pancreas (NP) and chronic pancreatitis (CP); 2) to validate reported diagnostic miR profiles in PC; 3) to discover new diagnostic miRs in pancreas samples without micro-dissection of cancer cells. Methods: MiR expression patterns in FFPE tissue blocks from patients operated for pancreatic ductal adenocarcinoma (PDAC, n=170) and ampullary adenocarcinomas (A-AC, n=107) were determined using TaqMan Human miR microarrray (Applied Biosystem; 754 miRs were determined) and compared to profiles of CP (n=23) and NP (n=28). Raw Ct-values were normalized using quantile-normalisation. Results: 83miRs were differentially expressed in PDAC and NP (42 higher expression; 41 reduced expression in PDAC). 32 miRs were differentially expressed in PDAC and CP. The most differentially expressed miRs were miR-614, miR-492, miR-622, miR-135b* and miR-196. The miR signatures of PDAC and A-AC were highly correlated (0.99; only 5 miRs were significantly differentially expressed). An earlier reported diagnostic miR profile for PDAC was validated (mirR196b - miR217), and 3 other significant profiles were identified (Table). A more complex Lasso classifier using 19 miRs could separate PDAC from NP and CP (accuracy = 98%). Conclusions: We identified systematic differences in patterns of miR expressions between tumor tissue including both cancer cells and surrounding desmoplasia obtained from patients with PDAC and A-AC compared to tissue from patients with CP and NP. We validated the diagnostic miR expression profile (miR-196b, miR-217) described by Szafranska et al. (Clin Chem 2008;54:1716-24). Furthermore, we identified 5 miRs which were better to discriminate PDAC and A-AC from CP and NP. Prospective studies are needed to evaluate if this panel of miRs is useful for early diagnosis of patients with PDAC. [Table: see text] No significant financial relationships to disclose.

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