The lung microenvironment: an important regulator of tumour growth and metastasis

Altorki, Nasser K.; Markowitz, Geoffrey J.; Gao, Dingcheng; Port, Jeffrey L.; Saxena, Ashish; Stiles, Brendon M.; McGraw, Timothy E.; Mittal, Vivek

doi:10.1038/s41568-018-0081-9

Cited by 813 publications

(680 citation statements)

References 287 publications

(247 reference statements)

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“…By detecting the expression of circRNA in patient tissues and cell lines, we found that circCDR1as expression was enhanced in NSCLC, indicating that high expression of circCDR1as could contribute to the malignancy of NSCLC. Tumor growth and metastasis are the two key regulators of lung cancer malignancy . To investigate the potential value of this circRNA in NSCLC, loss‐of‐function experiments were performed to confirm the anti‐proliferation and anti‐metastasis roles of circCDR1as silencing in NSCLC, which was similar to the previous report by Zhang et al .…”

Section: Discussionsupporting

confidence: 74%

“…Tumor growth and metastasis are the two key regulators of lung cancer malignancy. 29 To investigate the potential value of this circRNA in NSCLC, loss-of-function experiments were performed to confirm the anti-proliferation and anti-metastasis roles of circCDR1as silencing in NSCLC, which was similar to the previous report by Zhang et al 16 Moreover, epithelial-to-mesenchymal transition has been regarded as an important mechanism involved in the regulation of development and metastasis of lung cancer. 30,31 Hence, whether circCDR1as can promote cell growth, migration and invasion by inducing epithelial-tomesenchymal transition should be explored in the future.…”

Section: Discussionsupporting

confidence: 68%

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CircRNA CDR1as knockdown inhibits progression of non‐small‐cell lung cancer by regulating miR‐219a‐5p/SOX5 axis

Zhang

Pan

et al. 2020

Thoracic Cancer

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Background Circular RNAs (circRNAs) participate in the development of human cancers by regulating multiple cell processes. CircRNA antisense to the cerebellar degeneration‐related protein 1 transcript (circCDR1as) expression is dysregulated in many cancers, including non‐small‐cell lung cancer (NSCLC). However, the mechanism by which circCDR1as mediates the development of NSCLC remains unknown. Methods A total of 30 paired cancer and normal tissues were collected from patients with NSCLC. The expression levels of circCDR1as, microRNA (miR)‐219a‐5p and Sex determining region Y‐box protein 5 (SOX5) were measured in tissues or cells by quantitative real‐time polymerase chain reaction or western blot. Cell viability, apoptosis, migration and invasion were detected by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐tetrazolium bromide, colony formation, flow cytometry and transwell assays, respectively. The target relationship between miR‐219a‐5p and circCDR1as or SOX5 was validated by dual‐luciferase reporter assay. Results CircCDR1as expression was elevated in NSCLC tissues and cells in comparison to the matched controls. Interference of circCDR1as led to obvious inhibition of cell viability, migration and invasion and increase of apoptosis in NSCLC cells. MiR‐219a‐5p acted as a target of circCDR1as and miR‐219a‐5p downregulation attenuated the regulatory effect of circCDR1as silencing on NSCLC progression. Moreover, miR‐219a‐5p targeted SOX5 to repress the progression of NSCLC in vitro. Besides, circCDR1as knockdown reduced the expression of SOX5 by increasing miR‐219a‐5p level. Conclusion Knockdown of circCDR1as inhibited the progression of NSCLC by decreasing cell viability, migration and invasion and increasing apoptosis by upregulating miR‐219a‐5p and downregulating SOX5.

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Section: Discussionsupporting

confidence: 74%

Section: Discussionsupporting

confidence: 68%

CircRNA CDR1as knockdown inhibits progression of non‐small‐cell lung cancer by regulating miR‐219a‐5p/SOX5 axis

Zhang

Pan

et al. 2020

Thoracic Cancer

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“…[94] It has been treated as a new target, and many nanodrugs have been designed to respond to the tumor microenvironment, such as acidity and enzyme contents. Understanding the specific conditions of the tumor microenvironment may provide guidance for the treatment of tumors.…”

Section: Tumor Microenvironment-responsive Peptidesmentioning

confidence: 99%

“…Understanding the specific conditions of the tumor microenvironment may provide guidance for the treatment of tumors. [94] It has been treated as a new target, and many nanodrugs have been designed to respond to the tumor microenvironment, such as acidity and enzyme contents. [95] Recently, some specific peptides have been found to respond to the tumor microenvironment, and nanodrugs based on these peptides can undergo changes in the tumor microenvironment, such as structure and shape changes.…”

Section: Tumor Microenvironment-responsive Peptidesmentioning

confidence: 99%

Peptide‐Based Supramolecular Nanodrugs as a New Generation of Therapeutic Toolboxes against Cancer

Chang

Zou

Xing

et al. 2019

Advanced Therapeutics

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Peptides are an important class of biomaterials that are widely used in the biomedical field due to their biocompatibility, bioavailability, and structural diversity. They self-assemble into a variety of architectures by weak intermolecular interactions such as π-effects, van der Waals forces, ionic attraction, the hydrophobic effect, and hydrogen bonding, resulting in many advantages in cancer treatment. Self-assembling peptide nanostructures perform two functions: they act as nanocarriers to deliver drugs to tumor sites, and they regulate drug properties, for example, enhancing drug stability, improving the optical properties of photosensitizers, and increasing the immune response. This review focuses on peptide-based supramolecular nanodrugs or nanocarriers for different cancer treatment modalities, such as chemotherapy, phototherapy, and immunotherapy. In particular, peptides with special bioactive properties, such as tumor targeting, microenvironmental responsiveness, and antigenicity, will be highlighted for their utility in the effort to conquer cancer.

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“…Despite these technological advances, deep understanding of molecular mechanisms underlying development of complex lung pathologies is hindered by the heterogeneity of the lung microenvironment 20 and by changes in cellular number and composition during disease progression 14 , which cannot be resolved with bulk tissue studies. Hence, NGS-based approaches providing cellular resolution, like profiling of defined cell populations or single-cell analyses need to be implemented in order to identify cell types driving distinct disease phenotypes.…”

Section: Introductionmentioning

confidence: 99%

Versatile workflow for cell type resolved transcriptional and epigenetic profiles from cryopreserved human lung

Prada

Espinet

Mijosek

et al. 2020

Preprint

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47The complexity of the lung microenvironment together with changes in cellular 48 composition during disease progression make it exceptionally hard to understand the 49 molecular mechanisms leading to the development of chronic lung diseases. Although 50 recent advances in cell type resolved and single-cell sequencing approaches hold 51 great promise for studying complex diseases, their implementation greatly relies on 52 local access to fresh tissue, as traditional methods to process and store tissue do not 53 allow viable cell isolation. To overcome these hurdles, we developed a novel, versatile 54 workflow that allows long-term storage of human lung tissue with high cell viability, 55 permits thorough sample quality check before cell isolation, and is compatible with 56 next generation sequencing-based profiling, including single-cell approaches. We 57 demonstrate that cryopreservation is suitable for isolation of multiple cell types from 58 different lung locations and is applicable to both healthy and diseased tissue, including 59 COPD and tumor samples. Basal cells isolated from cryopreserved airways retain the 60 ability to differentiate, indicating that cellular identity is not altered by cryopreservation. 61 Importantly, using RNA sequencing (RNA-seq) and Illumina EPIC Array, we show that 62 genome-wide gene expression and DNA methylation signatures are preserved upon 63 cryopreservation, emphasizing the suitability of our workflow for -omics profiling of 64 human lung cells. In addition, we obtained high-quality single-cell RNA sequencing 65 data of cells isolated from cryopreserved human lung, demonstrating that 66 cryopreservation empowers single-cell approaches. Overall, thanks to its simplicity, 67 3 our cryopreservation workflow is well-suited for prospective tissue collection by 68 academic collaborators and biobanks, opening worldwide access to human tissue. 69 70

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The lung microenvironment: an important regulator of tumour growth and metastasis

Cited by 813 publications

References 287 publications

CircRNA CDR1as knockdown inhibits progression of non‐small‐cell lung cancer by regulating miR‐219a‐5p/SOX5 axis

CircRNA CDR1as knockdown inhibits progression of non‐small‐cell lung cancer by regulating miR‐219a‐5p/SOX5 axis

Peptide‐Based Supramolecular Nanodrugs as a New Generation of Therapeutic Toolboxes against Cancer

Versatile workflow for cell type resolved transcriptional and epigenetic profiles from cryopreserved human lung

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