Genome-wide CRISPR/Cas9 screening identifies CARHSP1 responsible for radiation resistance in glioblastoma

Zhu, Guodong; Yu, Jing; Sun, Zhengyu; Chen, Yan; Zheng, Hongmei; Lin, Mei-Lan; Ouyang, Shi; Liu, Guo-Long; Zhang, Jiewen; Shao, Fengmin

doi:10.1038/s41419-021-04000-3

Cited by 22 publications

(17 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, CARHSP1 was identified as a significant prognostic mRNA with the second-highest attention value. This result is also related to a recent study [ 54 ] that investigated whether CARHSP1 is radiotherapy protective in glioblastoma by signaling via the CARHSP1/TNF-α pathway. In addition, patients with high levels of CARHSP1 who are treated with radiotherapy have a poor prognosis.…”

Section: Discussionsupporting

confidence: 80%

Estimating the Prognosis of Low-Grade Glioma with Gene Attention Using Multi-Omics and Multi-Modal Schemes

Choi

Lee

2022

Biology

View full text Add to dashboard Cite

The prognosis estimation of low-grade glioma (LGG) patients with deep learning models using gene expression data has been extensively studied in recent years. However, the deep learning models used in these studies do not utilize the latest deep learning techniques, such as residual learning and ensemble learning. To address this limitation, in this study, a deep learning model using multi-omics and multi-modal schemes, namely the Multi-Prognosis Estimation Network (Multi-PEN), is proposed. When using Multi-PEN, gene attention layers are employed for each datatype, including mRNA and miRNA, thereby allowing us to identify prognostic genes. Additionally, recent developments in deep learning, such as residual learning and layer normalization, are utilized. As a result, Multi-PEN demonstrates competitive performance compared to conventional models for prognosis estimation. Furthermore, the most significant prognostic mRNA and miRNA were identified using the attention layers in Multi-PEN. For instance, MYBL1 was identified as the most significant prognostic mRNA. Such a result accords with the findings in existing studies that have demonstrated that MYBL1 regulates cell survival, proliferation, and differentiation. Additionally, hsa-mir-421 was identified as the most significant prognostic miRNA, and it has been extensively reported that hsa-mir-421 is highly associated with various cancers. These results indicate that the estimations of Multi-PEN are valid and reliable and showcase Multi-PEN’s capacity to present hypotheses regarding prognostic mRNAs and miRNAs.

show abstract

Section: Discussionsupporting

confidence: 80%

Estimating the Prognosis of Low-Grade Glioma with Gene Attention Using Multi-Omics and Multi-Modal Schemes

Choi

Lee

2022

Biology

View full text Add to dashboard Cite

show abstract

“…They further show that pharmacological activation of STING enhances the effects of ionizing radiation in vivo and might be a promising approach to enhance radiotherapeutic response in patients suffering from HNSCC (summarized in Table 1 ). In an interesting study, Zhu et al performed genome-wide CRISPR activation screening and identified calcium-regulated heat-stable protein 1 (CARHSP1) as an essential element involved in radioresistance traits in human glioblastoma cells (summarized in Table 1 ) [ 42 ]. Because of its cold-shock domain, CARHSP1 has the capacity to bind to polypyrimidine regions of single-stranded RNA, single-stranded DNA, or double-stranded DNA [ 59 ].…”

Section: High-throughput Screening Methods To Study Radiosensitivity ...mentioning

confidence: 99%

“…Intriguingly, CARHSP1 enhances mRNA stability of tumor necrosis factor-alpha (TNF-α), a crucial pleiotropic cytokine and a critical inflammatory molecule [ 60 ]. With this information, Zhu et al showed that an elevated level of CARHSP1 is associated with radioresistance of glioblastoma cells via CARHSP1/TNF-α pathway signaling [ 42 ]. Cheng et al used an unbiased genome-wide CRISPR/Cas9 knockout strategy in A549 lung cancer cells and identified plakophilin 2 (PKP2) as a critical driver of radiation resistance in lung cancer cells [ 61 ].…”

Section: High-throughput Screening Methods To Study Radiosensitivity ...mentioning

confidence: 99%

Identification of Novel Regulators of Radiosensitivity Using High-Throughput Genetic Screening

Tamaddondoust

Wong

Chandrashekhar

et al. 2022

IJMS

View full text Add to dashboard Cite

The biological impact of ionizing radiation (IR) on humans depends not only on the physical properties and absorbed dose of radiation but also on the unique susceptibility of the exposed individual. A critical target of IR is DNA, and the DNA damage response is a safeguard mechanism for maintaining genomic integrity in response to the induced cellular stress. Unrepaired DNA lesions lead to various mutations, contributing to adverse health effects. Cellular sensitivity to IR is highly correlated with the ability of cells to repair DNA lesions, in particular coding sequences of genes that affect that process and of others that contribute to preserving genomic integrity. However, accurate profiling of the molecular events underlying individual sensitivity requires techniques with sensitive readouts. Here we summarize recent studies that have used whole-genome analysis and identified genes that impact individual radiosensitivity. Whereas microarray and RNA-seq provide a snapshot of the transcriptome, RNA interference (RNAi) and CRISPR-Cas9 techniques are powerful tools that enable modulation of gene expression and characterizing the function of specific genes involved in radiosensitivity or radioresistance. Notably, CRISPR-Cas9 has altered the landscape of genome-editing technology with its increased readiness, precision, and sensitivity. Identifying critical regulators of cellular radiosensitivity would help tailor regimens that enhance the efficacy of therapeutic treatments and fast-track prediction of clinical outcomes. It would also contribute to occupational protection based on average individual sensitivity, as well as the formulation of countermeasures to the harmful effects of radiation.

show abstract

“…The underlying mechanism and changes in genes related to radiosensitivity were investigated further based on the results of clinical trials using common chemotherapy drugs combined with radiotherapy on three different bladder cancer cell lines (5637, TCCSUP, and J82). Zhu et al used the CRISPR/Cas9 SAM human lentiviral library, which contains 70,290 unique sgRNA sequences targeting 23,430 human genes, to screen the target genes related to radiotherapy sensitivity in neuroblastoma ( 9 ). Lan et al also used the CRISPR/Cas9 library to screen genes related to radiotherapy sensitivity in pancreatic cancer ( 10 ).…”

Section: Methodsmentioning

confidence: 99%

Differential expression of DNA damage repair genes after chemoradiotherapy and inhibition rate in different bladder cancer cells

Sun¹,

Jiang²,

Zeng³

2022

Transl Androl Urol

View full text Add to dashboard Cite

Background: To investigate the potential mechanisms of chemoradiotherapy resistance in patients with bladder cancer. Methods:We assessed three bladder cancer cell lines (5637, J82, and TCCSUP) for their sensitivity to chemoradiotherapy. Reverse transcription quantitative PCR (RT-qPCR) was used to detect the expression of specific genes after chemoradiotherapy or combined with olaparib. The Genome Cancer Atlas (TGCA) database was used to analyze possible radioresistance-related genes and the relationship between their expression and bladder cancer survival and prognostic indicators.Results: The 5637 cell line showed the most significant sensitivity to chemoradiotherapy. The expression levels of DNA damage repair genes in 5637 cells did not significantly change after chemoradiotherapy. In contrast, the expression levels of BRCA1 and RBBP8 genes significantly increased in J82 and TCCSUP cells after chemoradiotherapy. After combination with olaparib, which is a poly (ADP-ribose) polymerase inhibitor that initiates DNA repair, 5637 cells were significantly inhibited by chemoradiotherapy. However, chemoradiotherapy inhibition on J82 cells was weakened when combined with olaparib. A high reactive expression of BRCA1 and RBBP8 after combination with olaparib suggested that olaparib was ineffective because it did not induce synthetic lethality in which inhibiting PARP by olaparib coincided with suppression of BRCA1/2 expression result in cancer cell death. Conclusions:The expression levels of RBBP8 and BRCA1 genes were associated with sensitivity to radiotherapy and chemotherapy in bladder cancer, and an increase in reactive expression after treatment led to worse sensitivity. Therefore, the reactive expression levels of BRCA1 and RBBP8 after chemoradiotherapy may be useful in evaluating the efficacy of olaparib combination therapy.

show abstract

Genome-wide CRISPR/Cas9 screening identifies CARHSP1 responsible for radiation resistance in glioblastoma

Cited by 22 publications

References 39 publications

Estimating the Prognosis of Low-Grade Glioma with Gene Attention Using Multi-Omics and Multi-Modal Schemes

Estimating the Prognosis of Low-Grade Glioma with Gene Attention Using Multi-Omics and Multi-Modal Schemes

Identification of Novel Regulators of Radiosensitivity Using High-Throughput Genetic Screening

Differential expression of DNA damage repair genes after chemoradiotherapy and inhibition rate in different bladder cancer cells

Contact Info

Product

Resources

About