The mutational landscape of cancer’s vulnerability to ionizing radiation
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE216711 | GEO | 2022/10/30
REPOSITORIES: GEO
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Project description:We report the differential expression of circRNAs between T-BEAS-2B cells (cadmium-transformed BEAS-2B cells) and C-BEAS-2B cells (passage-matched control BEAS-2B cells) by high-throughput sequencing. T-BEAS-2B cells are BEAS-2B cells transformed by cadmium at 2.0 μM for twenty weeks, and C-BEAS-2B cells are their passage-matched control. RNAs were sequenced on Illumina HiSeq Xten platform in triplicates, and expressions of circRNAs were calculated by TPM (transcripts per kilobase of exon model per million mapped reads). Clean data per sample exceeds 10 GB. We find 235 significantly up-regulated circRNAs and 271 significantly down-regulated circRNAs in T-BEAS-2B cells relative to C-BEAS-2B cells. Our work provides clues and evidence for exploring the mechanism of circRNAs in cadmium carcinogenesis.
2024-01-26 | GSE165549 | GEO
Project description:To seek if ionizing radiation have different biological effect on lung normal cells and cancer cells, we treated lung epithelial cell line BEAS-2B, non-small cell lung cancer cell line A549 and small cell lung cancer cell line H446 with 10 Gy X-ray radiation
2022-12-31 | GSE211118 | GEO
Project description:The mutational landscape of cancer’s vulnerability to ionizing radiation
| PRJNA895034 | ENA
Project description:PurposeLarge-scale sequencing efforts have established that cancer-associated genetic alterations are highly diverse, posing a challenge to the identification of variants that regulate complex phenotypes like radiation sensitivity. The impact of the vast majority of rare or common genetic variants on the sensitivity of cancers to radiotherapy remains largely unknown.Experimental designWe developed a scalable gene editing and irradiation platform to assess the role of categories of variants in cells. Variants were prioritized on the basis of genotype-phenotype associations from a previously completed large-scale cancer cell line radiation profiling study. Altogether, 488 alleles (396 unique single-nucleotide variants) from 92 genes were generated and profiled in an immortalized lung cell line, BEAS-2B. We validated our results in other cell lines (TRT-HU1 and NCI-H520), in vivo via the use of both cell line and patient-derived murine xenografts, and in clinical cohorts.ResultsWe show that resistance to radiation is characterized by substantial inter- and intra-gene allelic variation. Some genes (e.g., KEAP1) demonstrated significant intragenic allelic variation in the magnitude of conferred resistance and other genes (e.g., CTNNB1) displayed both resistance and sensitivity in a protein domain-dependent manner. We combined results from our platform with gene expression and metabolite features and identified the upregulation of amino acid transporters that facilitate oxidative reductive capacity and cell-cycle deregulation as key regulators of radiation sensitivity.ConclusionsOur results reveal new insights into the genetic determinants of tumor sensitivity to radiotherapy and nominate a multitude of cancer mutations that are predicted to impact treatment efficacy.
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Project description:MicroRNA levels in non-transformed BEAS-2B bronchial epithelial cells, two lines of mycoplasma transformed BEAS-2B cells, and A549 lung adenocarcinoma cells were measured. Microarray analyses of 1145 microRNAs in A549 lung adenocarcinoma cells and two other transformed lung cell types relative to BEAS-2B bronchial epithelial cells were performed. 106 miRNAs were down-regulated and 69 miRNAs were up-regulated in all three transformed lines
2014-03-11 | GSE55748 | GEO
Project description:Total RNA samples from human bronchial epithelial BEAS-2B passage-matched control cells and Cr(VI)-transofmred BEAS-2B cells were submitted to ArraySatr for total RNA m6A epitranscriptomic microarray analysis
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Project description:The dismal lethality of lung cancer is due to late stage at diagnosis and inherent therapeutic resistance. The incorporation of targeted therapies has modestly improved clinical outcomes, but the identification of new targets could further improve clinical outcomes by guiding stratification of poor-risk early-stage patients and individualizing therapeutic choices. We hypothesized that a sequential, combined microarray approach would be valuable to identify and validate new targets in lung cancer. We profiled gene expression signatures during lung epithelial cell immortalization and transformation, and showed that genes involved in mitosis were progressively enhanced in carcinogenesis. 28 genes were validated by immunoblotting and 4 genes were further evaluated in non-small cell lung cancer tissue microarrays. Although CDK1 was highly expressed in tumor tissues, its loss from the cytoplasm unexpectedly predicted poor survival and conferred resistance to chemotherapy in multiple cell lines, especially microtubule-directed agents. An analysis of expression of CDK1 and CDK1-associated genes in the NCI60 cell line database confirmed the broad association of these genes with chemotherapeutic responsiveness. These results have implications for personalizing lung cancer therapy and highlight the potential of combined approaches for biomarker discovery. In these studies, we systematically profiled gene expression in normal (NHBE), immortalized (BEAS-2B) and fully transformed (NNK-BEAS-2B) human bronchial epithelial cells, as well as a non-small cell lung cancer (NSCLC) cell line (H157) from a smoker. Expression profiles that accompany the immortalization and/or transformation of bronchial epithelial cells were generated, and expression of 28 genes was validated by immunoblotting. 4 of them were further evaluated in immunohistochemical analyses of tissue microarrays that contain NSCLC specimens, surrounding non-diseased tissues and non-pulmonary normal tissues. Although all 4 genes were predominantly expressed in tumor tissues, loss of expression of cytoplasmic CDK1 was clinically important because it was associated with a poor prognosis for NSCLC patients. This poor prognostic value may be associated with therapeutic resistance because decreasing levels of cytoplasmic CDK1 in vitro increased resistance to standard chemotherapies used in the treatment of NSCLC, especially microtubule agents where resistance was almost complete. These studies illustrate how a combined microarray approach can facilitate the identification of new, relevant targets in cancer. Fluorescently labeled cDNA were synthesized from 100 microgram RNA by oligo(dT)-primed reverse transcription in the presence of Cy3- or Cy5-dUTP (Amersham Bisciences, Piscataway, NJ). Purified Cy3/Cy5-labelled probes were combined and hybridized in the presence of 2x Denhart's solution, 3.2x saline sodium citrate (SSC), and 0.5% sodium dodecyl sulfate (SDS) in a humidified chamber at 65°C overnight. Prior to scanning (Agilent Technologies, Foster City, CA), slides were successively washed at 22°C in 0.5x SSC/0.1% SDS for 2 min, 0.5x SSC/0.01% SDS for 2 min, and 0.06x SSC for 2 min. Image analyses were performed with the IPLab software (Fairfax, VA). The reference cell (NHBE) was included in every individual hybridization to allow for normalization of each clone’s expression relative to the reference for each cell line (BEAS-2B, NNK-BEAS-2B or H157). A self-to-self hybridization with dye reversal was performed to exclude preferential differences in probe labeling (not included here). Every sample was labeled with Cy5 and Cy3 and hybridized twice. The two fluorescent images (red and green channels) obtained from the scanner constituted the intensity raw data from which differential gene expression ratios and quality control values were calculated. All data were entered into a relational database, using the FileMaker Pro 5 software (Santa Clara, CA). Genes were identified as differentially regulated only if corrected red/green hybridization signals differed by at least two-fold. The genes in each group were alphabetically listed and the ratios of BEAS-2B/NHBE, NNK-BEAS-2B/NHBE or H157/NHBE were graphically visualized by Cluster and TreeView programs (http://rana.lbl.gov/EisenSoftware.htm). These methods fulfilled the MIAME criteria (http://www.mged.org/miame).
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2024-04-30 | GSE266289 | GEO
Project description:As environmental pollutants and possible carcinogens, carbon nanotubes (CNTs) have recently been found to promote tumorigenesis and tumor metastasis after long-term pulmonary exposure. However, whether CNT-induced carcinogenesis can be inherited and last for generations remains unknown. Here, we establish a post-chronic single-walled carbon nanotubes (SWCNTs) exposed human bronchial epithelium BEAS-2B cell model to investigate SWCNTs-induced carcinogenesis. At a tolerated sublethal dose level, post-chronic SWCNTs exposure significantly increases the migration and colony formation abilities of BEAS-2B cells, leading to cell malignant transformation. Notably, the malignant transformation of BEAS-2B cells is irreversible within 60 days recovery period after SWCNTs exposure, and the malignant transformation activities of cells gradually increase during the recovery period. Mechanism analyses show that post-chronic exposure to SWCNTs causes substantial DNA methylation and transcriptome dysregulation of BEAS-2B cells. Subsequent enrichment and clinical database analyses reveal that differentially expressed/methylated genes of BEAS-2B cells are enriched in cancer-related biological pathways, and several of these genes are validated in lung cancer patients. As environmental pollutants and possible carcinogens, carbon nanotubes (CNTs) have recently been found to promote tumorigenesis and tumor metastasis after long-term pulmonary exposure. However, whether CNT-induced carcinogenesis can be inherited and last for generations remains unknown. Here, we establish a post-chronic single-walled carbon nanotubes (SWCNTs) exposed human bronchial epithelium BEAS-2B cell model to investigate SWCNTs-induced carcinogenesis. At a tolerated sublethal dose level, post-chronic SWCNTs exposure significantly increases the migration and colony formation abilities of BEAS-2B cells, leading to cell malignant transformation. Notably, the malignant transformation of BEAS-2B cells is irreversible within 60 days recovery period after SWCNTs exposure, and the malignant transformation activities of cells gradually increase during the recovery period. Mechanism analyses show that post-chronic exposure to SWCNTs causes substantial DNA methylation and transcriptome dysregulation of BEAS-2B cells. Subsequent enrichment and clinical database analyses reveal that differentially expressed/methylated genes of BEAS-2B cells are enriched in cancer-related biological pathways, and several of these genes are validated in lung cancer patients.
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