Transplacental Lung Carcinogenesis: A Pharmacogenetic Mouse Model for the Modulatory Role of Cytochrome P450 1A1 on Lung Cancer Initiation

AbstractLung cancer is the leading cause of cancer-associated deaths accounting for 24% of all cancer deaths. As a crucial phase of tumor progression, lung cancer metastasis is linked to over 70% of these mortalities. In recent years, exosomes have received increasing research attention in their role in the induction of carcinogenesis and metastasis in the lung. In this review, recent studies on the contribution of exosomes to lung cancer metastasis are discussed, particularly highlighting the role of lung tumor-derived exosomes in immune system evasion, epithelial-mesenchymal transition, and angiogenesis, and their involvement at both the pre-metastatic and metastatic phases. The clinical application of exosomes as therapeutic drug carriers, their role in antitumor drug resistance, and their utility as predictive biomarkers in diagnosis and prognosis are also presented. The metastatic activity, a complex multistep process of cancer cell invasion, survival in blood vessels, attachment and subsequent colonization of the host's organs, is integrated with exosomal effects. Exosomes act as functional mediating factors in cell–cell communication, influencing various steps of the metastatic cascade. To this end, lung cancer cell-derived exosomes enhance cell proliferation, angiogenesis, and metastasis, regulate drug resistance, and antitumor immune activities during lung carcinogenesis, and are currently being explored as an important component in liquid biopsy assessment for diagnosing lung cancer. These nano-sized extracellular vesicles are also being explored as delivery vehicles for therapeutic molecules owing to their unique properties of biocompatibility, circulatory stability, decreased toxicity, and tumor specificity. The current knowledge of the role of exosomes highlights an array of exosome-dependent pathways and cargoes that are ripe for exploiting therapeutic targets to treat lung cancer metastasis, and for predictive value assessment in diagnosis, prognosis, and anti-tumor drug resistance.

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Role of microRNAs in Lung Carcinogenesis Induced by Asbestos

Journal of Personalized Medicine ◽

10.3390/jpm11020097 ◽

2021 ◽

Vol 11 (2) ◽

pp. 97

Author(s):

Rakhmetkazhy Bersimbaev ◽

Olga Bulgakova ◽

Akmaral Aripova ◽

Assiya Kussainova ◽

Oralbek Ilderbayev

Keyword(s):

Lung Cancer ◽

Expression Profile ◽

Regulation Of Gene Expression ◽

International Agency ◽

Oxygen Species ◽

Lung Carcinogenesis ◽

Mrna Targets ◽

The World ◽

Post Transcriptional Regulation

MicroRNAs are a class of small noncoding endogenous RNAs 19–25 nucleotides long, which play an important role in the post-transcriptional regulation of gene expression by targeting mRNA targets with subsequent repression of translation. MicroRNAs are involved in the pathogenesis of numerous diseases, including cancer. Lung cancer is the leading cause of cancer death in the world. Lung cancer is usually associated with tobacco smoking. However, about 25% of lung cancer cases occur in people who have never smoked. According to the International Agency for Research on Cancer, asbestos has been classified as one of the cancerogenic factors for lung cancer. The mechanism of malignant transformation under the influence of asbestos is associated with the genotoxic effect of reactive oxygen species, which initiate the processes of DNA damage in the cell. However, epigenetic mechanisms such as changes in the microRNA expression profile may also be implicated in the pathogenesis of asbestos-induced lung cancer. Numerous studies have shown that microRNAs can serve as a biomarker of the effects of various adverse environmental factors on the human body. This review examines the role of microRNAs, the expression profile of which changes upon exposure to asbestos, in key processes of carcinogenesis, such as proliferation, cell survival, metastasis, neo-angiogenesis, and immune response avoidance.

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Differential Impacts of Insulin-Like Growth Factor-Binding Protein-3 (IGFBP-3) in Epithelial IGF-Induced Lung Cancer Development

Endocrinology ◽

10.1210/en.2010-0693 ◽

2011 ◽

Vol 152 (6) ◽

pp. 2164-2173 ◽

Cited By ~ 13

Author(s):

Woo-Young Kim ◽

Mi-Jung Kim ◽

Hojin Moon ◽

Ping Yuan ◽

Jin-Soo Kim ◽

...

Keyword(s):

Lung Cancer ◽

Lung Tumor ◽

Binding Protein ◽

Cancer Development ◽

Lung Carcinogenesis ◽

Tobacco Carcinogen ◽

Igf I ◽

The Impact ◽

Igfbp 3

The IGF axis has been implicated in the risk of various cancers. We previously reported a potential role of tissue-derived IGF in lung tumor formation and progression. However, the role of IGF-binding protein (IGFBP)-3, a major IGFBP, on the activity of tissue-driven IGF in lung cancer development is largely unknown. Here, we show that IGF-I, but not IGF-II, protein levels in non-small-cell lung cancer (NSCLC) were significantly higher than those in normal and hyperplastic bronchial epithelium. We found that IGF-I and IGFBP-3 levels in NSCLC tissue specimens were significantly correlated with phosphorylated IGF-IR (pIGF-IR) expression. We investigated the impact of IGFBP-3 expression on the activity of tissue-driven IGF-I in lung cancer development using mice carrying lung-specific human IGF-I transgene (Tg), a germline-null mutation of IGFBP-3, or both. Compared with wild-type (BP3+/+) mice, mice carrying heterozygous (BP3+/−) or homozygous (BP3−/−) deletion of IGFBP-3 alleles exhibited decreases in circulating IGFBP-3 and IGF-I. Unexpectedly, IGFTg mice with 50% of physiological IGFBP-3 (BP3+/−; IGFTg) showed higher levels of pIGF-IR/IR and a greater degree of spontaneous or tobacco carcinogen [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone]-induced lung tumor development and progression than did the IGFTg mice with normal (BP3+/+;IGFTg) or homozygous deletion of IGFBP-3 (BP3−/−; IGFTg). These data show that IGF-I is overexpressed in NSCLC, leading to activation of IGF-IR, and that IGFBP-3, depending on its expression level, either inhibits or potentiates IGF-I actions in lung carcinogenesis.

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The Role of microRNAs in the Regulation of Apoptosis in Lung Cancer and Its Application in Cancer Treatment

BioMed Research International ◽

10.1155/2014/318030 ◽

2014 ◽

Vol 2014 ◽

pp. 1-19 ◽

Cited By ~ 26

Author(s):

Norahayu Othman ◽

Noor Hasima Nagoor

Keyword(s):

Lung Cancer ◽

Cancer Progression ◽

High Frequency ◽

Tumor Suppressor Genes ◽

Molecular Mechanisms ◽

Lung Carcinogenesis ◽

The Past ◽

Late Stage Diagnosis ◽

Anticancer Treatment

Lung cancer remains to be one of the most common and serious types of cancer worldwide. While treatment is available, the survival rate of this cancer is still critically low due to late stage diagnosis and high frequency of drug resistance, thus highlighting the pressing need for a greater understanding of the molecular mechanisms involved in lung carcinogenesis. Studies in the past years have evidenced that microRNAs (miRNAs) are critical players in the regulation of various biological functions, including apoptosis, which is a process frequently evaded in cancer progression. Recently, miRNAs were demonstrated to possess proapoptotic or antiapoptotic abilities through the targeting of oncogenes or tumor suppressor genes. This review examines the involvement of miRNAs in the apoptotic process of lung cancer and will also touch on the promising evidence supporting the role of miRNAs in regulating sensitivity to anticancer treatment.

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Role of Cytochrome P450 3A4 and 1A2 Phenotyping in Patients with Advanced Non-small-Cell Lung Cancer Receiving Erlotinib Treatment

Basic & Clinical Pharmacology & Toxicology ◽

10.1111/bcpt.12801 ◽

2017 ◽

Vol 121 (4) ◽

pp. 309-315 ◽

Cited By ~ 7

Author(s):

Zinnia P. Parra-Guillen ◽

Peter B. Berger ◽

Manuel Haschke ◽

Massimiliano Donzelli ◽

Daria Winogradova ◽

...

Keyword(s):

Lung Cancer ◽

Cytochrome P450 ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Cytochrome P450 3A4 ◽

Small Cell Lung

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Determination of the Role of Target Tissue Metabolism in Lung Carcinogenesis Using Conditional Cytochrome P450 Reductase-Null Mice

Cancer Research ◽

10.1158/0008-5472.can-07-1006 ◽

2007 ◽

Vol 67 (16) ◽

pp. 7825-7832 ◽

Cited By ~ 64

Author(s):

Yan Weng ◽

Cheng Fang ◽

Robert J. Turesky ◽

Melissa Behr ◽

Laurence S. Kaminsky ◽

...

Keyword(s):

Cytochrome P450 ◽

Target Tissue ◽

Cytochrome P450 Reductase ◽

Lung Carcinogenesis ◽

Tissue Metabolism ◽

P450 Reductase

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The Role of MicroRNAs in Lung Cancer: Implications for Diagnosis and Therapy

Current Molecular Medicine ◽

10.2174/1566524019666191001113511 ◽

2020 ◽

Vol 20 (2) ◽

pp. 90-101 ◽

Cited By ~ 14

Author(s):

Parisa Naeli ◽

Fatemeh Yousefi ◽

Younes Ghasemi ◽

Amir Savardashtaki ◽

Hamed Mirzaei

Keyword(s):

Lung Cancer ◽

High Rate ◽

Small Noncoding Rnas ◽

Non Invasive ◽

Egfr Signaling Pathway ◽

High Prevalence ◽

Cancer Initiation ◽

Pathway Regulation ◽

Noninvasive Biomarkers

: Lung cancer is the first cause of cancer death in the world due to its high prevalence, aggressiveness, late diagnosis, lack of effective treatment and poor prognosis. It also shows high rate of recurrence, metastasis and drug resistance. All these problems highlight the urgent needs for developing new strategies using noninvasive biomarkers for early detection, metastasis and recurrence of disease. MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate gene expression post-transcriptionally. These molecules found to be abnormally expressed in increasing number of human disease conditions including cancer. miRNAs could be detected in body fluids such as blood, serum, urine and sputum, which leads us towards the idea of using them as non-invasive biomarker for cancer detection and monitoring cancer treatment and recurrence. miRNAs are found to be deregulated in lung cancer initiation and progression and could regulate lung cancer cell proliferation and invasion. In this review, we summarized recent progress and discoveries in microRNAs regulatory role in lung cancer initiation and progression. In addition, the role of microRNAs in EGFR signaling pathway regulation is discussed briefly.

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