CircRNAs in Lung Adenocarcinoma: Diagnosis and Therapy

Su, Lijia; Zhao, Jinying; Su, Huahua; Wang, Yanhua; Huang, Wenfeng; Jiang, Xuemei; Gao, Songxin

doi:10.2174/1566523221666211202095258

Cited by 12 publications

(11 citation statements)

References 73 publications

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“…In recent decades, much attention has been paid on the molecular mechanisms underlying the pathogenesis of LUAD, and the epigenetic alternations and gene mutations take up an important reason contributing to the regulation of LUAD development. [20][21][22] In the present study, we demonstrated aberrant upregulation of NPAS2 and ARRB1 in LUAD cell lines. ARRB1 was found to be a critical transcription factor of NPAS2 with binding sites within the promoter region of NPAS2, thereby causing its transcriptional activation.…”

Section: Discussionsupporting

confidence: 64%

“…LUAD has become a great threat to public health, accompanied by increased morbidity and mortality in women worldwide. In recent decades, much attention has been paid on the molecular mechanisms underlying the pathogenesis of LUAD, and the epigenetic alternations and gene mutations take up an important reason contributing to the regulation of LUAD development 20–22 . In the present study, we demonstrated aberrant upregulation of NPAS2 and ARRB1 in LUAD cell lines.…”

Section: Discussionsupporting

confidence: 61%

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NPAS2, transcriptionally activated by ARRB1, promotes the malignant behaviours of lung adenocarcinoma cells and regulates the reprogramming of glucose metabolism

Wang,

Huang,

Zheng

et al. 2024

Clin Exp Pharma Physio

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Lung adenocarcinoma (LUAD) is a serious threat to public health and is accompanied by increased morbidity and mortality worldwide. Neuronal PAS domain protein2 (NPAS2) has been confirmed as an oncogene in LUAD; however, little is known about its molecular mechanism. Here, the expression level of NPAS2 was detected in LUAD cell lines and 16HBE cells. Gain‐ and loss‐of‐function experiments were performed. Cell Counting Kit‐8, colony formation, flow cytometry, wound‐healing and Transwell assays were conducted to assess cell proliferation, apoptosis, migration and invasion, respectively. Reprogramming of glucose metabolism was evaluated via oxygen consumption rate (OCR), complexes activities, lactic production and glucose consumption. The expression of critical proteins was examined by western blot. We demonstrated aberrant upregulation of NPAS2 and β‐arrestin‐1 (ARRB1) in LUAD cell lines. ARRB1 was found to be a critical transcription factor of NPAS2 with binding sites within the promoter region of NPAS2, thereby causing its transcriptional activation. Functional experiments revealed that NPAS2 depletion significantly inhibited the malignant behaviours of A549 cells by suppressing cell proliferation, migration, invasion and epithelial‐mesenchymal transition and promoting cell apoptosis. Meanwhile, NPAS2 depletion increased OCR and activities of complexes (I, II, III and V), and reduced lactic acid production and glucose uptake in A549 cells, indicating that NPAS2 depletion inhibited aerobic glycolysis, accompanied by reduced expression of glycolytic enzymes. However, the changes caused by NPAS2 knockdown were partly restored by ARRB1 overexpression. In conclusion, our study suggests that ARRB1 could transcriptionally activate NPAS2, facilitating malignant activities and glycolysis, and ultimately promoting the progression of LUAD, proving a novel therapeutic strategy for the treatment of LUAD.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionsupporting

confidence: 61%

NPAS2, transcriptionally activated by ARRB1, promotes the malignant behaviours of lung adenocarcinoma cells and regulates the reprogramming of glucose metabolism

Wang,

Huang,

Zheng

et al. 2024

Clin Exp Pharma Physio

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“…This is likely due to the fact that lung adenocarcinoma can infiltrate and grow into the bronchial cavity, adjacent lung tissue, and other organs, as well as spreading to other sites through lymphatic and hematogenous routes. Therefore, most patients are difficult to be diagnosed at an early stage and are often reached when detected, leading to a poor prognosis ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

Non-targeted metabolomics analysis of indoleamine 2,3-dioxygenase inhibitor treatment in a mouse model of early-stage lung adenocarcinoma

Xu,

Chen,

Peng

et al. 2024

Transl Cancer Res

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Background Lung adenocarcinoma is a common malignant tumor, and its early diagnosis and treatment are key to improving patient survival rates. However, due to the non-specific early symptoms, many patients are already at an advanced stage when diagnosed. Non-targeted metabolomics analysis, as a method for comprehensive analysis of metabolites in the body, has been shown to have potential in the early diagnosis of cancer. This study aims to identify early-stage lung adenocarcinoma-specific biomarkers using non-targeted metabolomics analysis in an established mouse model. The intervention mechanism of indoleamine 2,3-dioxygenase (IDO) inhibitor in early-stage lung adenocarcinoma is explored to provide evidence for clinical disease treatment. Methods Twenty specific-pathogen-free-grade female Kunming mice were divided into control group, experimental group, Epacadostatlow group, and Epacadostathigh group. After modeling, immune therapy intervention (epacadostat) was administered to the mice, and plasma and urine samples were collected from all mice on day 7 and day 28. Ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) analysis was performed to identify potential biomarkers for diagnosing early-stage lung adenocarcinoma. Cluster analysis and correlation analysis were used to explore the differential expression patterns of metabolites in different samples. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was used to identify enriched pathways of differentially expressed metabolites. Results A total of 348 metabolites were identified after merging the positive and negative ion modes. Among them, organic acids and derivatives (16.954%) and lipids and lipid-like molecules (15.517%) were the two major classes of metabolites in the early-stage lung adenocarcinoma mice. Anthranilic acid (vitamin L1), 1-methylhistidine, 12(R)-HETE, and hippuric acid were the major differentially expressed metabolites on both day 7 and day 28, and they showed correlations with each other. Metabolic pathway analysis revealed multiple dysregulated pathways in lung adenocarcinoma mice. Conclusions UPLC-QTOF-MS analysis is a feasible method for identifying biomarkers of lung adenocarcinoma. Epacadostat, a novel and promising IDO inhibitor, may exert its therapeutic effect by modulating 1-methylhistidine and anthranilic acid (vitamin L1).

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“…Lung adenocarcinoma (LUAD) is a common type of non‐small cell lung cancer (NSCLC) that originates in the bronchial mucosal epithelium and is more common in nonsmoking women 1,2 . Despite these efforts, there is still much room for improvement in the treatment options for LUAD patients 3,4 .…”

Section: Introductionmentioning

confidence: 99%

Tumor‐related exosomal circ_0001715 promotes lung adenocarcinoma cell proliferation and metastasis via enhancing M2 macrophage polarization by regulating triggering receptor expressed on myeloid cells‐2

Chen,

Cao,

2023

Thoracic Cancer

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BackgroundCircular RNAs (circRNAs) have been shown to mediate tumor‐associated macrophages (TAMs) to regulate the development of many cancers, including lung adenocarcinoma (LUAD). However, whether circ_0001715 regulates LUAD progression by mediating TAMs polarization remains uncertain.MethodsMonocytes (THP‐1) were treated with PMA to induce M0 macrophages. M0 macrophages were incubated with LUAD cells‐derived exosomes and then cocultured with LUAD cells. The levels of circ_0001715, M2 macrophage markers, microRNA (miR)‐205‐5p, and triggering receptor expressed on myeloid cells‐2 (TREM2) were examined using quantitative real‐time PCR. Flow cytometry was performed to assess M2 macrophage surface marker CD206. Cell proliferation, migration and invasion were determined using cell counting kit 8, EdU, colony formation and transwell assays. Dual‐luciferase reporter assay was used to investigate the interactions between miR‐205‐5p and circ_0001715 or TREM2.ResultsCirc_0001715 knockdown inhibited M2 macrophage polarization and its overexpression had an opposite effect. After M0 macrophages transfected with si‐circ_0001715 were cocultured with LUAD cells, the proliferation and metastasis of LUAD cells were markedly reduced. Exosomes transferred circ_0001715 between M0 macrophages and LUAD cells. Exosomal circ_0001715 promoted M2 macrophage polarization to increase LUAD cell proliferation and metastasis. In terms of mechanism, circ_0001715 sponged miR‐205‐5p to positively regulate TREM2. TREM2 upregulation also could promote LUAD cell proliferation and metastasis via increasing M2 macrophage polarization. In addition, TREM2 knockdown reversed the effect of exosomal circ_0001715 on M2 macrophage polarization and LUAD cell progression.ConclusionExosomal circ_0001715 led to LUAD cell proliferation and metastasis by promoting M2 macrophage polarization via the miR‐205‐5p/TREM2 axis.

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CircRNAs in Lung Adenocarcinoma: Diagnosis and Therapy

Cited by 12 publications

References 73 publications

NPAS2, transcriptionally activated by ARRB1, promotes the malignant behaviours of lung adenocarcinoma cells and regulates the reprogramming of glucose metabolism

NPAS2, transcriptionally activated by ARRB1, promotes the malignant behaviours of lung adenocarcinoma cells and regulates the reprogramming of glucose metabolism

Non-targeted metabolomics analysis of indoleamine 2,3-dioxygenase inhibitor treatment in a mouse model of early-stage lung adenocarcinoma

Tumor‐related exosomal circ_0001715 promotes lung adenocarcinoma cell proliferation and metastasis via enhancing M2 macrophage polarization by regulating triggering receptor expressed on myeloid cells‐2

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