|
1
|
Liang H, Deng J, Luo T, Luo H, Li F, Wu K, Lin C. Chromatin accessibility reveals potential prognostic value of the peak set associated with smoking history in patients with lung adenocarcinoma. Heliyon 2024; 10:e41006. [PMID: 39720074 PMCID: PMC11665461 DOI: 10.1016/j.heliyon.2024.e41006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Revised: 12/03/2024] [Accepted: 12/04/2024] [Indexed: 12/26/2024] Open
Abstract
Considerable differences in molecular characteristics have been defined between non-smoker and smokers in patients with lung adenocarcinoma (LUAD), yet studies on open chromatin patterns associated with LUAD progression caused by smoking are still lacking. Here, we constructed a novel network based on correlations between each ATAC-seq peak from TCGA data using our previously developed algorithm. Subsequently, principal component analysis was performed on LUAD samples with retained peaks filtered by the correlation network, and pathway analysis was conducted to identify potential pathways involved. We identified a set of peaks that discriminated smokers in LUAD patients according to levels of exposure to tobacco quantified in pack-years. These peaks were also significantly associated with progression-free survival and overall survival of these patients. Further examination of the gene set related to those peaks revealed that the comprising genes, such as KRT19, B3GNT3, CLDN7 and CLDN3 are strongly associated with LUAD development. They are consistent with the important roles of the associated pathways in LUAD oncogenesis induced by smoking, including estrogen response, apical junction and glycolysis pathways. In summary, our study may provide valuable insights into exploring ATAC-seq peaks and understanding smoking-related LUAD carcinogenesis from a perspective of open chromatin changes.
Collapse
Affiliation(s)
- Han Liang
- HIM-BGI Omics Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences (CAS), BGI Research, Hangzhou 310000, China
- Guangdong Provincial Key Laboratory of Human Disease Genomics, BGI Research, Shenzhen 518083, China
- BGI Genomics, Shenzhen 518083, China
| | - Jianlian Deng
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Tian Luo
- HIM-BGI Omics Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences (CAS), BGI Research, Hangzhou 310000, China
- BGI Genomics, Shenzhen 518083, China
| | - Huijuan Luo
- HIM-BGI Omics Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences (CAS), BGI Research, Hangzhou 310000, China
- BGI Genomics, Shenzhen 518083, China
| | - Fuqiang Li
- HIM-BGI Omics Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences (CAS), BGI Research, Hangzhou 310000, China
- Guangdong Provincial Key Laboratory of Human Disease Genomics, BGI Research, Shenzhen 518083, China
- BGI Genomics, Shenzhen 518083, China
| | - Kui Wu
- HIM-BGI Omics Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences (CAS), BGI Research, Hangzhou 310000, China
- Guangdong Provincial Key Laboratory of Human Disease Genomics, BGI Research, Shenzhen 518083, China
- BGI Genomics, Shenzhen 518083, China
| | - Cong Lin
- HIM-BGI Omics Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences (CAS), BGI Research, Hangzhou 310000, China
- Guangdong Provincial Key Laboratory of Human Disease Genomics, BGI Research, Shenzhen 518083, China
- BGI Genomics, Shenzhen 518083, China
| |
Collapse
|
|
2
|
Balasundaram A, C Doss GP. Deciphering the Impact of Rare Missense Variants in EGFR-TKI-Resistant Non-Small-Cell Lung Cancer through Whole Exome Sequencing: A Computational Approach. ACS OMEGA 2024; 9:16288-16302. [PMID: 38617633 PMCID: PMC11007825 DOI: 10.1021/acsomega.3c10229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Revised: 02/21/2024] [Accepted: 02/26/2024] [Indexed: 04/16/2024]
Abstract
Targeted therapy revolutionizes the treatment of non-small-cell lung cancer (NSCLC), harboring molecular change. Epidermal growth factor receptor(EGFR) mutations play a crucial role in the development of NSCLC, serving as a pivotal factor in its pathogenesis. We elucidated the mechanisms of resistance and potential therapeutic strategies in NSCLC resistant to the EGFR-tyrosine kinase inhibitor (EGFR-TKI). This is achieved by identifying rare missense variants through whole exome sequencing (WES). The goal is to enhance our understanding, identify biomarkers, and lay the groundwork for targeted interventions, thereby offering hope for an improved NSCLC treatment landscape. We conducted WES analysis on 16 NSCLC samples with EGFR-TKI-resistant NSCLC obtained from SRA-NCBI (PRJEB50602) to reveal genomic profiles within the EGFR-TKI. Our findings showed that 48% of the variants were missense, and after filtering with the Ensembl variant effect predictor, 53 rare missense variants in 23 genes were identified as highly deleterious. Further examination using pathogenic tools like PredictSNP revealed 12 deleterious rare missense variants in 7 genes: ZNF717, PSPH, ESRRA, SEMA3G, PTPN7, CAVIN4, and MYBBP1A. Molecular dynamics simulation (MDS) suggested that the L385P variant alters the structural flexibility of ESRRA, potentially leading to unfolding of ERRα proteins. This could impact their function and alter ERRα expression. These insights from MDS enhance our understanding of the structural and dynamic consequences of the L385P ESRRA variant and provide valuable implications for subsequent therapeutic considerations and targeted interventions.
Collapse
Affiliation(s)
- Ambritha Balasundaram
- Laboratory of Integrative
Genomics, Department of Integrative Biology, School of BioSciences
and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu 632014, India
| | - George Priya C Doss
- Laboratory of Integrative
Genomics, Department of Integrative Biology, School of BioSciences
and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu 632014, India
| |
Collapse
|
|
3
|
Vanacker JM, Forcet C. ERRα: unraveling its role as a key player in cell migration. Oncogene 2024; 43:379-387. [PMID: 38129506 DOI: 10.1038/s41388-023-02899-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 10/31/2023] [Accepted: 11/14/2023] [Indexed: 12/23/2023]
Abstract
Cell migration is essential throughout the life of multicellular organisms, and largely depends on the spatial and temporal regulation of cytoskeletal dynamics, cell adhesion and signal transduction. Interestingly, Estrogen-related receptor alpha (ERRα) has been identified as a major regulator of cell migration in both physiological and pathological conditions. ERRα is an orphan member of the nuclear hormone receptor superfamily of transcription factors and displays many biological functions. ERRα is a global regulator of energy metabolism, and it is also highly involved in bone homeostasis, development, differentiation, immunity and cancer progression. Importantly, in some instances, the regulation of these biological processes relies on the ability to orchestrate cell movements. Therefore, this review describes how ERRα-mediated cell migration contributes not only to tissue homeostasis but also to tumorigenesis and metastasis, and highlights the molecular and cellular mechanisms by which ERRα finely controls the cell migratory potential.
Collapse
Affiliation(s)
- Jean-Marc Vanacker
- Centre de Recherche en Cancérologie de Lyon, CNRS UMR5286, Inserm U1052, Université de Lyon, Lyon, France
| | - Christelle Forcet
- Institut de Génomique Fonctionnelle de Lyon, UMR5242, Ecole Normale Supérieure de Lyon, Centre National de la Recherche Scientifique, Université Claude Bernard-Lyon 1, Lyon, France.
| |
Collapse
|
|
4
|
Rodriguez-Lara V, Soca-Chafre G, Avila-Costa MR, Whaley JJJV, Rodriguez-Cid JR, Ordoñez-Librado JL, Rodriguez-Maldonado E, Heredia-Jara NA. Role of sex and sex hormones in PD-L1 expression in NSCLC: clinical and therapeutic implications. Front Oncol 2023; 13:1210297. [PMID: 37941543 PMCID: PMC10628781 DOI: 10.3389/fonc.2023.1210297] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Accepted: 09/28/2023] [Indexed: 11/10/2023] Open
Abstract
Currently, immunotherapy based on PD-1/PD-L1 pathway blockade has improved survival of non-small cell lung cancer (NSCLC) patients. However, differential responses have been observed by sex, where men appear to respond better than women. Additionally, adverse effects of immunotherapy are mainly observed in women. Studies in some types of hormone-dependent cancer have revealed a role of sex hormones in anti-tumor response, tumor microenvironment and immune evasion. Estrogens mainly promote immune tolerance regulating T-cell function and modifying tumor microenvironment, while androgens attenuate anti-tumor immune responses. The precise mechanism by which sex and sex hormones may modulate immune response to tumor, modify PD-L1 expression in cancer cells and promote immune escape in NSCLC is still unclear, but current data show how sexual differences affect immune therapy response and prognosis. This review provides update information regarding anti-PD-1/PD-L immunotherapeutic efficacy in NSCLC by sex, analyzing potential roles for sex hormones on PD-L1 expression, and discussing a plausible of sex and sex hormones as predictive response factors to immunotherapy.
Collapse
Affiliation(s)
- Vianey Rodriguez-Lara
- Department of Cell and Tissue Biology, Faculty of Medicine, UNAM, Mexico City, Mexico
| | - Giovanny Soca-Chafre
- Oncological Diseases Research Unit (UIEO), Hospital Infantil de México Federico Gómez, Mexico City, Mexico
| | - Maria Rosa Avila-Costa
- Neuromorphology Laboratory, Facultad de Estudios Superiores Iztacala, UNAM, Mexico City, Mexico
| | | | | | | | - Emma Rodriguez-Maldonado
- Traslational Medicine Laboratory, Research Unit UNAM-INC, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
| | | |
Collapse
|
|
5
|
Zhong S, Borlak J. Sex disparities in non-small cell lung cancer: mechanistic insights from a cRaf transgenic disease model. EBioMedicine 2023; 95:104763. [PMID: 37625265 PMCID: PMC10470261 DOI: 10.1016/j.ebiom.2023.104763] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Revised: 07/10/2023] [Accepted: 08/03/2023] [Indexed: 08/27/2023] Open
Abstract
BACKGROUND Women are at greater risk of developing non-small cell lung cancer (NSCLC), yet the underlying causes remain unclear. METHODS We performed whole genome scans in lung tumours of cRaf transgenic mice and identified miRNA, transcription factor and hormone receptor dependent gene regulations. We confirmed hormone receptors by immunohistochemistry and constructed regulatory gene networks by considering experimentally validated miRNA-gene and transcription factor-miRNA/gene targets. Bioinformatics, genomic foot-printing and gene enrichment analysis established sex-specific circuits of lung tumour growth. Translational research involved a large cohort of NSCLC patients. We evaluated commonalities in sex-specific NSCLC gene regulations between mice and humans and determined their prognostic value in Kaplan-Meier survival statistics and COX proportional hazard regression analysis. FINDINGS Overexpression of the cRaf kinase elicited an extraordinary 8-fold increase in tumour growth among females, and nearly 70% of the 112 differentially expressed genes (DEGs) were female specific. We identified oncogenes, oncomirs, tumour suppressors, cell cycle regulators and MAPK/EGFR signalling molecules, which prompted sex-based differences in NSCLC, and we deciphered a regulatory gene-network, which protected males from accelerated tumour growth. Strikingly, 41% of DEGs are targets of hormone receptors, and the majority (85%) are oestrogen receptor (ER) dependent. We confirmed the role of ER in a large cohort of NSCLC patients and validated 40% of DEGs induced by cRaf in clinical tumour samples. INTERPRETATION We report the molecular wiring that prompted sex disparities in tumour growth. This allowed us to propose the development of molecular targeted therapies by jointly blocking ER, CDK1 and arginase 2 in NSCLC. FUNDING We gratefully acknowledge the financial support of the Lower Saxony Ministry of Culture and Sciences and Volkswagen Foundation, Germany to JB (25A.5-7251-99-3/00) and of the Chinese Scholarship Council to SZ (202008080022). This publication is funded by the Deutsche Forschungsgemeinschaft (DFG) as part of the "Open Access Publikationskosten" program.
Collapse
Affiliation(s)
- Shen Zhong
- Centre for Pharmacology and Toxicology, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany
| | - Jürgen Borlak
- Centre for Pharmacology and Toxicology, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
| |
Collapse
|
|
6
|
Adrenocortical Carcinoma (ACC) Cells Rewire Their Metabolism to Overcome Curcumin Antitumoral Effects Opening a Window of Opportunity to Improve Treatment. Cancers (Basel) 2023; 15:cancers15041050. [PMID: 36831394 PMCID: PMC9954484 DOI: 10.3390/cancers15041050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 01/31/2023] [Accepted: 02/04/2023] [Indexed: 02/11/2023] Open
Abstract
Extensive research suggests that curcumin interferes with multiple cell signaling pathways involved in cancer development and progression. This study aimed to evaluate curcumin effects on adrenocortical carcinoma (ACC), a rare but very aggressive tumor. Curcumin reduced growth, migration and activated apoptosis in three different ACC cell lines, H295R, SW13, MUC-1. This event was related to a decrease in estrogen-related receptor-α (ERRα) expression and cholesterol synthesis. More importantly, curcumin changed ACC cell metabolism, increasing glycolytic gene expression. However, pyruvate from glycolysis was only minimally used for lactate production and the Krebs cycle (TCA). In fact, lactate dehydrogenase, extracellular acidification rate (ECAR), TCA genes and oxygen consumption rate (OCR) were reduced. We instead found an increase in Glutamic-Pyruvic Transaminase (GPT), glutamine antiport transporter SLC1A5 and glutaminase (GLS1), supporting a metabolic rewiring toward glutamine metabolism. Targeting this mechanism, curcumin effects were improved. In fact, in a low glutamine-containing medium, the growth inhibitory effects elicited by curcumin were observed at a concentration ineffective in default growth medium. Data from this study prove the efficacy of curcumin against ACC growth and progression and point to the concomitant use of inhibitors for glutamine metabolism to improve its effects.
Collapse
|
|
7
|
Yang D, Li S, Zhao D, Zou T, Liu X, Pang J, Zhuang W, Yan Z. Secondary growth synthesis of covalent organic framework modified electrospun nanofibers for extraction of estrogens in milk samples. J Food Compost Anal 2023. [DOI: 10.1016/j.jfca.2023.105222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/16/2023]
|
|
8
|
Nowińska K, Jabłońska K, Ciesielska U, Piotrowska A, Haczkiewicz-Leśniak K, Pawełczyk K, Podhorska-Okołów M, Dzięgiel P. Association of Irisin/FNDC5 with ERRα and PGC-1α Expression in NSCLC. Int J Mol Sci 2022; 23:ijms232214204. [PMID: 36430689 PMCID: PMC9694131 DOI: 10.3390/ijms232214204] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 11/10/2022] [Accepted: 11/14/2022] [Indexed: 11/18/2022] Open
Abstract
The rapid growth and division of cancer cells are associated with mitochondrial biogenesis or switching to glycolysis. ERRα, PGC-1α and irisin/FNDC5 are some of the proteins that can influence these processes. The aim of this study was to determine the correlation of these proteins in non-small cell lung cancer (NSCLC) and to investigate their association with clinicopathological parameters. Immunohistochemistry reactions were performed on tissue microarrays (860 NSCLC, 140 non-malignant lung tissue). The normal fibroblast cell line (IMR-90) and lung cancer cell lines (NCI-H1703 and NCI-H522) were used as co-cultures. The mRNA levels of FNDC5 and ESRRA (encoding ERRα) were assessed in IMR-90 cells after co-culture with lung cancer cells. We observed a decreased level of ERRα with an increase in tumor size (T), stages of the disease, and lymph node metastases (N). In the adenocarcinoma (AC) subtype, patients with a higher ERRα expression had significantly longer overall survival. A moderate positive correlation was observed between FNDC5 mRNA and ESRRA mRNA in NSCLCs. The expression of FNDC5 mRNA in IMR-90 cells increased after 24 h, and ESRRA gene expression increased after 48 h of co-culture. The ERRα receptor with PGC-1α participates in the control of FNDC5/irisin expression. Normal fibroblasts revealed an upregulation of the FNDC5 and ESRRA genes under the influence of lung cancer cells.
Collapse
Affiliation(s)
- Katarzyna Nowińska
- Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland
- Correspondence:
| | - Karolina Jabłońska
- Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland
| | - Urszula Ciesielska
- Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland
| | - Aleksandra Piotrowska
- Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland
| | | | - Konrad Pawełczyk
- Lower Silesian Centre of Oncology, Pulmonology and Haematology, 53-439 Wroclaw, Poland
| | - Marzenna Podhorska-Okołów
- Division of Ultrastructural Research, Wroclaw Medical University, 50-368 Wroclaw, Poland
- Department of Physiotherapy, Wroclaw University School of Physical Education, 51-612 Wroclaw, Poland
| | - Piotr Dzięgiel
- Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland
- Department of Physiotherapy, Wroclaw University School of Physical Education, 51-612 Wroclaw, Poland
| |
Collapse
|
|
9
|
Estrogen Related Receptor Alpha (ERRα) a Bridge between Metabolism and Adrenocortical Cancer Progression. Cancers (Basel) 2022; 14:cancers14163885. [PMID: 36010877 PMCID: PMC9406166 DOI: 10.3390/cancers14163885] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 08/01/2022] [Accepted: 08/08/2022] [Indexed: 11/17/2022] Open
Abstract
Simple Summary Adrenocortical carcinoma (ACC) is a rare and highly aggressive tumor associated with a very poor prognosis, mostly due to a high risk of recurrence and limited therapeutic options. The identification of “master regulators” of the metabolic changes occurring in cancer cells could offer new targets for innovative therapies. Such a strategy has never been used against ACC progression. In this study, we identify ERRα as key player in ACC metabolism and its targeting can prevent progression to a more aggressive phenotype. The development of new therapeutic strategies to selectively target ERRα in the adrenal with a selective antagonist would hinder ACC progression, avoiding off-target effects. Abstract The aim of this study was to investigate the metabolic changes that occur in adrenocortical cancer (ACC) cells in response to the modulation of Estrogen Related Receptor (ERR)α expression and the impact on ACC progression. Proteomics analysis and metabolic profiling highlighted an important role for ERRα in the regulation of ACC metabolism. Stable ERRα overexpression in H295R cells promoted a better mitochondrial fitness and prompted toward a more aggressive phenotype characterized by higher Vimentin expression, enhanced cell migration and spheroids formation. By contrast, a decrease in ERRα protein levels, by molecular (short hairpin RNA) and pharmacological (inverse agonist XCT790) approaches modified the energetic status toward a low energy profile and reduced Vimentin expression and ability to form spheroids. XCT790 produced similar effects on two additional ACC cell lines, SW13 and mitotane-resistant MUC-1 cells. Our findings show that ERRα is able to modulate the metabolic profile of ACC cells, and its inhibition can strongly prevent the growth of mitotane-resistant ACC cells and the progression of ACC cell models to a highly migratory phenotype. Consequently, ERRα can be considered an important target for the design of new therapeutic strategies to fight ACC progression.
Collapse
|
|
10
|
Yu J, He X, Fang C, Wu H, Hu L, Xue Y. MicroRNA‑200a‑3p and GATA6 are abnormally expressed in patients with non‑small cell lung cancer and exhibit high clinical diagnostic efficacy. Exp Ther Med 2022; 23:281. [PMID: 35317445 PMCID: PMC8908458 DOI: 10.3892/etm.2022.11210] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Accepted: 11/16/2021] [Indexed: 11/15/2022] Open
Abstract
Lung cancer is one of the main threats to human health. Survival of patients with lung cancer depends on timely detection and diagnosis. Among the genetic irregularities that control cancer development and progression, there are microRNAs (miRNAs/miRs). The present study aimed to investigate the expression patterns of miR-200a-3p and transcription factor GATA-6 (GATA6) in peripheral blood of patients with non-small cell lung cancer (NSCLC) and their clinical significance. The expression patterns of miR-200a-3p and GATA6 in the peripheral blood of patients with NSCLC and healthy subjects were measured via reverse transcription-quantitative PCR. The correlation between GATA6/miR-200a-3p expression and their diagnostic efficacy were analyzed by receiver operating characteristic curve analysis. The association between miR-200a-3p/GATA6 expression with the patient clinicopathological characteristics, and their correlation with carcinoembryonic antigen (CEA), neuron specific enolase (NSE) and squamous cell carcinoma antigen (SCCAg) were evaluated. The cumulative survival rate was examined, and whether miR-200a-3p and GATA6 expression levels were independently correlated with the prognosis of NSCLC was analyzed using multivariate logistic regression model. The results demonstrated that the expression of miR-200a-3p was high and that of GATA6 was low in the peripheral blood of patients with NSCLC, and both exhibited high clinical diagnostic efficacy. miR-200a-3p was revealed to target GATA6 by dual-luciferase assay. miR-200a-3p in the peripheral blood was correlated with TNM stage, lymph node metastasis and distal metastasis, while GATA6 in the peripheral blood was correlated with TNM stage and lymph node metastasis. miR-200a-3p and GATA6 were positively correlated with CEA and SCCAg, but not with NSE. High expression of miR-200a-3p and low expression of GATA6 predicted poor prognosis in patients with NSCLC. After adjusting for TNM stage, lymph node metastasis, distance metastasis, GATA6, CEA, NSE and SCCAg in the logistic regression model, it was indicated that the high expression of miR-200a-3p increased the risk of death in patients with NSCLC. Collectively, it was revealed that miR-200a-3p and GATA6 were abnormally expressed in the peripheral blood of patients with NSCLC. Serum levels of miR-200a-3p >1.475 and GATA6 <1.195 may assist the early diagnosis of NSCLC. GATA6 may function in NSCLC as a miR-200a-3p target, which may provide a future reference for NSCLC early diagnosis and treatment.
Collapse
Affiliation(s)
- Jie Yu
- Department of Oncology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550001, P.R. China
| | - Xinyun He
- Department of Oncology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550001, P.R. China
| | - Chunju Fang
- Department of Oncology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550001, P.R. China
| | - Haixia Wu
- Department of Oncology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550001, P.R. China
| | - Lei Hu
- Department of Laboratory Medicine, Guizhou Women's and Children's Hospital, Guiyang, Guizhou 550003, P.R. China
| | - Yingbo Xue
- Department of Oncology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550001, P.R. China
| |
Collapse
|
|
11
|
Sahebnasagh A, Saghafi F, Negintaji S, Hu T, Shabani-Borujeni M, Safdari M, Ghaleno HR, Miao L, Qi Y, Wang M, Liao P, Sureda A, Simal-Gándara J, Nabavi SM, Xiao J. Nitric Oxide and Immune Responses in Cancer: Searching for New Therapeutic Strategies. Curr Med Chem 2022; 29:1561-1595. [PMID: 34238142 DOI: 10.2174/0929867328666210707194543] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 05/05/2021] [Accepted: 05/15/2021] [Indexed: 02/08/2023]
Abstract
In recent years, there has been an increasing interest in understanding the mysterious functions of nitric oxide (NO) and how this pleiotropic signaling molecule contributes to tumorigenesis. This review attempts to expose and discuss the information available on the immunomodulatory role of NO in cancer and recent approaches to the role of NO donors in the area of immunotherapy. To address the goal, the following databases were searched to identify relevant literature concerning empirical evidence: The Cochrane Library, Pubmed, Medline, and EMBASE from 1980 through March 2020. Valuable attempts have been made to develop distinctive NO-based cancer therapy. Although the data do not allow generalization, the evidence seems to indicate that low/moderate levels may favor tumorigenesis, while higher levels would exert antitumor effects. In this sense, the use of NO donors could have an important therapeutic potential within immunotherapy, although there are still no clinical trials. The emerging understanding of NO-regulated immune responses in cancer may help unravel the recent features of this "doubleedged sword" in cancer physiological and pathologic processes and its potential use as a therapeutic agent for cancer treatment. In short, in this review, we discuss the complex cellular mechanism in which NO, as a pleiotropic signaling molecule, participates in cancer pathophysiology. We also debate the dual role of NO in cancer and tumor progression and clinical approaches for inducible nitric oxide synthase (iNOS) based therapy against cancer.
Collapse
Affiliation(s)
- Adeleh Sahebnasagh
- Clinical Research Center, Department of Internal Medicine, Faculty of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Fatemeh Saghafi
- Department of Clinical Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Sina Negintaji
- Student Research Committee, School of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Tingyan Hu
- School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong
| | - Mojtaba Shabani-Borujeni
- Department of Clinical Pharmacy, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammadreza Safdari
- Department of Orthopedic Surgery, Faculty of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Hassan Rezai Ghaleno
- Department of Surgery, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Lingchao Miao
- Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao
| | - Yaping Qi
- Purdue Quantum Science and Engineering Institute, Purdue University, West Lafayette, IN 47907, USA
| | - Mingfu Wang
- School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong
| | - Pan Liao
- Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA
| | - Antoni Sureda
- Research Group on Community Nutrition and Oxidative Stress, and Balearic Islands Health Research Institute (IdISBa), University of the Balearic Islands, Palma de Mallorca, Spain
- CIBEROBN (Physiopathology of Obesity and Nutrition CB12/03/30038), Instituto de Salud Carlos III, Madrid, Spain
| | - Jesus Simal-Gándara
- Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Food Science and Technology, University of Vigo - Ourense Campus, E-32004 Ourense, Spain
| | - Seyed Mohammad Nabavi
- Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Jianbo Xiao
- Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Food Science and Technology, University of Vigo - Ourense Campus, E-32004 Ourense, Spain
- International Research Centre for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China
| |
Collapse
|
|
12
|
Targeting Estrogens and Various Estrogen-Related Receptors against Non-Small Cell Lung Cancers: A Perspective. Cancers (Basel) 2021; 14:cancers14010080. [PMID: 35008242 PMCID: PMC8750572 DOI: 10.3390/cancers14010080] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 12/08/2021] [Accepted: 12/16/2021] [Indexed: 12/20/2022] Open
Abstract
Non-small cell lung cancers (NSCLCs) account for ~85% of lung cancer cases worldwide. Mammalian lungs are exposed to both endogenous and exogenous estrogens. The expression of estrogen receptors (ERs) in lung cancer cells has evoked the necessity to evaluate the role of estrogens in the disease progression. Estrogens, specifically 17β-estradiol, promote maturation of several tissue types including lungs. Recent epidemiologic data indicate that women have a higher risk of lung adenocarcinoma, a type of NSCLC, when compared to men, independent of smoking status. Besides ERs, pulmonary tissues both in healthy physiology and in NSCLCs also express G-protein-coupled ERs (GPERs), epidermal growth factor receptor (EGFRs), estrogen-related receptors (ERRs) and orphan nuclear receptors. Premenopausal females between the ages of 15 and 50 years synthesize a large contingent of estrogens and are at a greater risk of developing NSCLCs. Estrogen-ER/GPER/EGFR/ERR-mediated activation of various cell signaling molecules regulates NSCLC cell proliferation, survival and apoptosis. This article sheds light on the most recent achievements in the elucidation of sequential biochemical events in estrogen-activated cell signaling pathways involved in NSCLC severity with insight into the mechanism of regulation by ERs/GPERs/EGFRs/ERRs. It further discusses the success of anti-estrogen therapies against NSCLCs.
Collapse
|