LungCancer3D: A Comprehensive Database for Integrating Lung Cancer Chromatin Architecture with Other Multi-omics

With the breakthrough of chromatin conformation capture technologies in recent years, the importance of three-dimensional (3D) genome structure in gene expression, cell function regulation, disease occurrence, and development has been gradually recognized. To provide a comprehensive visualization of chromatin architecture and other multi-omics data for lung cancer research, we have constructed a comprehensive database, LungCancer3D (http://www.lungcancer3d.net). This web-based tool focuses on displaying human lung cancer-related HiC data along with a variety of other publicly available data, such as RNA-seq, scRNA-seq, ATAC-seq, ChIP-seq, DNA methylation, DNA mutation, and copy number variations. Researchers can visualize these diverse multi-omics data directly through the genome browser and discover how the genes expression is regulated at diverse levels. For example, we have demonstrated that the high expression level of C-MYC in lung cancer may be caused by the distant enhancer introduced by the de novo chromatin loops in lung cancer cells to bind the C-MYC promoter. The integrated multi-omics analyses through the LungCancer3D website can reveal the mechanisms underlying lung cancer development and provide potential targets for lung cancer therapy.

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A new Pb(II)-based coordination polymer constructed from a semirigid tricarboxylate ligand: crystal structure and anti-lung cancer activity

Main Group Metal Chemistry ◽

10.1515/mgmc-2018-0034 ◽

2019 ◽

Vol 42 (1) ◽

pp. 8-12

Author(s):

Kun-Ning Yang ◽

Ke-De Yuan ◽

Li-Li Jiang ◽

Yong Zhang

Keyword(s):

Lung Cancer ◽

Coordination Polymer ◽

Ultrasonic Method ◽

Three Dimensional ◽

Human Lung Cancer ◽

X Ray Diffraction ◽

Dioic Acid ◽

X Ray ◽

The One ◽

Solvothermal Conditions

Abstract Based on a semirigid tricarboxylate ligand 5-((4-carboxyphenoxy)methyl)benzene-1,3-dioic acid (H3L), a new Pb(II)-based coordination polymer formulated as [Pb(HL)(H2O)](H2O) (1) was synthesized under solvothermal conditions and characterized by single-crystal X-ray structural analysis, power X-ray diffraction, and elemental analysis. Compound 1 is a two-dimensional layered structure formed by the connection of the one-dimensional Pb(II)-based secondary building unit chains with the partly deprotonated HL ligands, which are further extended into three-dimensional supermolecular structures through the H-bonds. Furthermore, the size of the as-prepared 1 could be downsized into the nano region through a simple ultrasonic method. Finally, the antilung cancer activities of 1 and the nanosized 1 have been probed via the MTT assay against three human lung cancer cell lines (A549, H1299, and PC9).

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Bioengineering three-dimensional culture model of human lung cancer cells: an improved tool for screening EGFR targeted inhibitors

RSC Advances ◽

10.1039/c6ra00229c ◽

2016 ◽

Vol 6 (29) ◽

pp. 24083-24090 ◽

Cited By ~ 13

Author(s):

Dan-Dan Wang ◽

Wei Liu ◽

Jing-Jie Chang ◽

Xu Cheng ◽

Xiu-Zhen Zhang ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

Human Lung ◽

Three Dimensional ◽

Lung Cancer Cells ◽

Human Lung Cancer ◽

Culture Model ◽

Human Lung Cancer Cells ◽

Targeted Inhibitors ◽

Three Dimensional Culture

Bioengineering a three-dimensional culture model of human lung cancer cells for screening EGFR targeted inhibitors.

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Anticancer Activity of Ipomoea purpurea Leaves Extracts in Monolayer and Three-Dimensional Cell Culture

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/6666567 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

F. Beheshti ◽

A. A. Shabani ◽

M. R. Akbari Eidgahi ◽

P. Kookhaei ◽

M. Vazirian ◽

...

Keyword(s):

Breast Cancer ◽

Lung Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Three Dimensional ◽

Human Lung Cancer ◽

Phase Cell ◽

Ipomoea Purpurea ◽

Organic Extracts

Cancer is a leading cause of death and a vital health care challenge in the world. Hence, this work was conducted to determine the in vitro anticancer property and also the molecular mechanism of aqueous and organic extracts of Ipomoea purpurea leaves in three human cancer cell lines, including A-549 (human lung cancer), HepG-2 (human liver cancer), MDA-MB-231 (human breast cancer), and MCF-10A (breast normal cell line). In vitro cytotoxic potential of organic extracts, such as hexane, chloroform, ethyl-acetate, methanol, and aqueous extract was examined using a standard (3-(4,5-dimethylthiazole)-2,5-diphenyltetrazolium bromide) MTT method in both monolayer two-dimensional (2D) and spheroids multicellular three-dimensional (3D) cultures. The MTT assay data showed that methanol and chloroform extracts of I. purpurea leaves had the antiproliferative effect on lung and breast cancer cells with IC50 of 53.62 ± 0.07 and 124.5 ± 0.01 µg/mL, respectively. The results of further examinations, such as dual acridine orange/ethidium bromide, Annexin V-FITC/PI, and caspase-3 colorimetric assay, confirmed that methanol and chloroform extracts of I. purpurea as the most potent cytotoxic extracts might contain a variety of phytochemicals, promoting apoptosis in lung and breast cancer cells. The present research findings suggested that methanolic extract of I. purpurea leaves induced S-phase cell cycle arrest and intrinsic pathway of apoptosis in A-549 lung cancer cells. The study further showed that I. purpurea could be a helpful candidate for cancer treatment.

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The lung-enriched p53 mutants V157F and R158L/P regulate a gain of function transcriptome in lung cancer

Carcinogenesis ◽

10.1093/carcin/bgz087 ◽

2019 ◽

Vol 41 (1) ◽

pp. 67-77 ◽

Cited By ~ 1

Author(s):

Julie A Barta ◽

Kristen Pauley ◽

Andrew V Kossenkov ◽

Steven B McMahon

Keyword(s):

Lung Cancer ◽

Tumor Suppressor ◽

Target Genes ◽

Human Lung ◽

De Novo ◽

Human Lung Cancer ◽

Migration And Invasion ◽

Mutant P53 ◽

P53 Mutations ◽

Gain Of Function

Abstract Lung cancer is the leading cause of cancer-related deaths in the USA, and alterations in the tumor suppressor gene TP53 are the most frequent somatic mutation among all histologic subtypes of lung cancer. Mutations in TP53 frequently result in a protein that exhibits not only loss of tumor suppressor capability but also oncogenic gain-of-function (GOF). The canonical p53 hotspot mutants R175H and R273H, for example, confer upon tumors a metastatic phenotype in murine models of mutant p53. To the best of our knowledge, GOF phenotypes of the less often studied V157, R158 and A159 mutants—which occur with higher frequency in lung cancer compared with other solid tumors—have not been defined. In this study, we aimed to define whether the lung mutants are simply equivalent to full loss of the p53 locus, or whether they additionally acquire the ability to drive new downstream effector pathways. Using a publicly available human lung cancer dataset, we characterized patients with V157, R158 and A159 p53 mutations. In addition, we show here that cell lines with mutant p53-V157F, p53-R158L and p53-R158P exhibit a loss of expression of canonical wild-type p53 target genes. Furthermore, these lung-enriched p53 mutants regulate genes not previously linked to p53 function including PLAU. Paradoxically, mutant p53 represses genes associated with increased cell viability, migration and invasion. These findings collectively represent the first demonstration that lung-enriched p53 mutations at V157 and R158 regulate a novel transcriptome in human lung cancer cells and may confer de novo function.

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Association of Copy Number Variations in Autism Spectrum Disorders: A Systematic Review

Chinese Journal of Biology ◽

10.1155/2014/713109 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 8

Author(s):

Elif Funda Sener

Keyword(s):

Autism Spectrum Disorders ◽

Complex Traits ◽

Copy Number ◽

De Novo ◽

Genome Structure ◽

Autism Spectrum ◽

Copy Number Variations ◽

Repetitive Behaviors ◽

Wide Range ◽

Spectrum Disorders

Autism spectrum disorders (ASDs) are characterized by language impairments, social deficits, and repetitive behaviors. The onset of symptoms occurs by the age of 3 and shows a lifelong persistence. Genetics plays a major role in the etiology of ASD. Except genetics, several potential risk factors (environmental factors and epigenetics) may contribute to ASD. Copy number variations (CNVs) are the most widespread structural variations in the human genome. These variations can alter the genome structure either by deletion or by duplication. CNVs can be de novo or inherited. Chromosomal rearrangements have been detected in 5–10% of the patients with ASD and recently copy number changes ranging from a few kilobases (kb) to several megabases (Mb) in size have been reported. Recent data have also revealed that submicroscopic CNVs can have a role in ASD, and de novo CNVs seem to be a more common risk factor in sporadic compared with inherited forms of ASD. CNVs are being implicated as a contributor to the pathophysiology of complex neurodevelopmental disorders and they can affect a wide range of human phenotypes including mental retardation (MR), autism, neuropsychiatric disorders, and susceptibility to other complex traits such as HIV, Crohn’s disease, and psoriasis. This review emphasizes the major CNVs reported to date in ASD.

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De novo synthesis of serine and glycine fuels purine nucleotide biosynthesis in human lung cancer tissues

Journal of Biological Chemistry ◽

10.1074/jbc.ra119.008743 ◽

2019 ◽

Vol 294 (36) ◽

pp. 13464-13477 ◽

Cited By ~ 15

Author(s):

Teresa W. M. Fan ◽

Ronald C. Bruntz ◽

Ye Yang ◽

Huan Song ◽

Yelena Chernyavskaya ◽

...

Keyword(s):

Lung Cancer ◽

Human Lung ◽

De Novo ◽

Human Lung Cancer ◽

Purine Nucleotide ◽

De Novo Synthesis ◽

Nucleotide Biosynthesis ◽

Cancer Tissues

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In vivo miRNA knockout screening identifies miR-190b as a novel tumor suppressor

PLoS Genetics ◽

10.1371/journal.pgen.1009168 ◽

2020 ◽

Vol 16 (11) ◽

pp. e1009168

Author(s):

Hui Hong ◽

Shun Yao ◽

Yuanyuan Zhang ◽

Yi Ye ◽

Cheng Li ◽

...

Keyword(s):

Lung Cancer ◽

Tumor Suppressor ◽

Mouse Model ◽

Human Lung ◽

De Novo ◽

Malignant Progression ◽

Human Lung Cancer ◽

Lung Tumorigenesis ◽

Genetically Engineered Mouse Model

MicroRNAs (miRNAs) play important roles in the development of various cancers including lung cancer which is one of the devastating diseases worldwide. How miRNAs function in de novo lung tumorigenesis remains largely unknown. We here developed a CRISPR/Cas9-mediated dual guide RNA (dgRNA) system to knockout miRNAs in genetically engineered mouse model (GEMM). Through bioinformatic analyses of human lung cancer miRNA database, we identified 16 downregulated miRNAs associated with malignant progression and performed individual knockout with dgRNA system in KrasG12D/Trp53L/L (KP) mouse model. Using this in vivo knockout screening, we identified miR-30b and miR-146a, which has been previously reported as tumor suppressors and miR-190b, a new tumor-suppressive miRNA in lung cancer development. Over-expression of miR-190b in KP model as well as human lung cancer cell lines significantly suppressed malignant progression. We further found that miR-190b targeted the Hus1 gene and knockout of Hus1 in KP model dramatically suppressed lung tumorigenesis. Collectively, our study developed an in vivo miRNA knockout platform for functionally screening in GEMM and identified miR-190b as a new tumor suppressor in lung cancer.

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