Genome-Scale CRISPR Knockout Screening Identifies BACH1 as a Key Regulator of Aflatoxin B1-Induced Oxidative Damage

Zhang, Jinfu; Hu, Shengyong; Zhao, Changzhi; Zhou, Yuan; Zhang, Lu; Liu, Hailong; Zhou, Peng; Li, Sheng; Fu, Liangliang; Zheng, Zhuqing; Xiang, Yue; Xu, Xuewen; Ruan, Jinxue; Li, Xinyun; Sun, Luo; Cao, Gang; Song, Zhao; Wang, Xu; Xie, Shengsong

doi:10.3390/antiox11091787

Cited by 12 publications

(10 citation statements)

References 34 publications

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“…CRISPR-Cas9 is a precise and efficient gene-editing tool that can be rapidly and widely applied in researching gene function and improving economically important traits such as muscle quality, fiber length, coat color, and litter size [ 30 ]. Genome-wide CRISPR-Cas9 knockout technology has been applied to humans [ 31 ], mice [ 32 ], pigs [ 33 ], chickens [ 34 ], cattle other animals. Shalem et al [ 35 ] performed genome-wide CRISPR-Cas9 knockout of 18,080 target genes and 64,751 gDNAs in humans to identify genes required for the growth and survival of cancer and pluripotent stem cells while screening out genes associated with vemurafenib resistance.…”

Section: Discussionmentioning

confidence: 99%

Massively Parallel CRISPR-Cas9 Knockout Screening in Sheep Granulosa Cells for FSH Response Genes

Liu,

Dai,

Sun

et al. 2024

Animals

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Follicle-stimulating hormone (FSH) regulates ovarian follicle development through specific gene expression programs. Granulosa cells (GCs) are somatic cells surrounding the oocytes, secreting gonadotropins to regulate ovulation and promote follicular development. By analyzing the effects of different doses of FSH on the proliferation of GCs, we found that adding 10 ng/mL of FSH, as the optimal concentration, could promote the growth of GCs. Furthermore, we have successfully constructed the first CRISPR-Cas9 knockout library targeting the genes on chromosomes 2 and 3 and the X chromosomes of the sheep massively parallel coding gene, as well as an ovarian GCs knockout cell library. For the first time, we have exposed the knockout cell library to a concentration of 10 ng/mL FSH to explore the underlying mechanisms. Through this screening, we have identified 836 positive–negative screening genes that are responsive to FSH, thereby revealing the regulatory mechanisms and screening the functionality of candidate genes. Next, RNA-Seq of control (0 ng/mL), low (10 ng/mL), and high (100 ng/mL) doses of FSH revealed 1708 differentially expressed genes, and combined with 836 genes, we obtained 129 FSH dose-dependent genes with extremely significant differences. This enables us to delve deeper into investigating and identifying the mechanisms by which FSH regulates GCs. More generally, we have discovered new regulatory factors and identified reproductivity-associated major effectors. These findings provide novel research directions for further studies on sheep reproduction.

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Section: Discussionmentioning

confidence: 99%

Massively Parallel CRISPR-Cas9 Knockout Screening in Sheep Granulosa Cells for FSH Response Genes

Liu,

Dai,

Sun

et al. 2024

Animals

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“…HPPE is an effective mimic of heme and has higher safety, which makes it a potential treatment for Parkinson’s disease. Based on virtual structural screening, the small molecule 1-piperazineethanol, α-[(1,3-benzodioxol-5-yloxy) methyl] -4-(2-methoxyphenyl) (M2) was identified as an inhibitor of BACH1 and effectively reduced aflatoxin B 1 -induced oxidative damage [ 146 ]. However, the research on these BACH1 inhibitors is still at the stage of in vitro experiments or animal models, while their bioavailability and safety need to be further explored.…”

Section: Bach1 As a Therapeutic Targetmentioning

confidence: 99%

Transcription factor BACH1 in cancer: roles, mechanisms, and prospects for targeted therapy

Hu,

Zhang,

Luo

et al. 2024

Biomark Res

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Transcription factor BTB domain and CNC homology 1 (BACH1) belongs to the Cap ‘n’ Collar and basic region Leucine Zipper (CNC-bZIP) family. BACH1 is widely expressed in mammalian tissues, where it regulates epigenetic modifications, heme homeostasis, and oxidative stress. Additionally, it is involved in immune system development. More importantly, BACH1 is highly expressed in and plays a key role in numerous malignant tumors, affecting cellular metabolism, tumor invasion and metastasis, proliferation, different cell death pathways, drug resistance, and the tumor microenvironment. However, few articles systematically summarized the roles of BACH1 in cancer. This review aims to highlight the research status of BACH1 in malignant tumor behaviors, and summarize its role in immune regulation in cancer. Moreover, this review focuses on the potential of BACH1 as a novel therapeutic target and prognostic biomarker. Notably, the mechanisms underlying the roles of BACH1 in ferroptosis, oxidative stress and tumor microenvironment remain to be explored. BACH1 has a dual impact on cancer, which affects the accuracy and efficiency of targeted drug delivery. Finally, the promising directions of future BACH1 research are prospected. A systematical and clear understanding of BACH1 would undoubtedly take us one step closer to facilitating its translation from basic research into the clinic.

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“…BACH1 deficiency reduces AFB1-induced liver oxidative damage by upregulating antioxidant genes. A kind of small molecule inhibitor of BACH1, named 1-Piperazineethanol, α-[(1,3-benzodioxol-5-yloxy) methyl]-4-(2-methoxyphenyl) (M2), ameliorates AFB1-induced human cell death in vitro and liver injury in vivo ( Zhang et al, 2022 ). These findings suggest that BACH1 contributes to acute and chronic liver injury.…”

Section: Bach Proteins and Benign Diseases Of The Digestive Systemmentioning

confidence: 99%

Pathophysiological role of BACH transcription factors in digestive system diseases

et al. 2023

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BTB and CNC homologous (BACH) proteins, including BACH1 and BACH2, are transcription factors that are widely expressed in human tissues. BACH proteins form heterodimers with small musculoaponeurotic fibrosarcoma (MAF) proteins to suppress the transcription of target genes. Furthermore, BACH1 promotes the transcription of target genes. BACH proteins regulate physiological processes, such as the differentiation of B cells and T cells, mitochondrial function, and heme homeostasis as well as pathogenesis related to inflammation, oxidative-stress damage caused by drugs, toxicants, or infections; autoimmunity disorders; and cancer angiogenesis, epithelial-mesenchymal transition, chemotherapy resistance, progression, and metabolism. In this review, we discuss the function of BACH proteins in the digestive system, including the liver, gallbladder, esophagus, stomach, small and large intestines, and pancreas. BACH proteins directly target genes or indirectly regulate downstream molecules to promote or inhibit biological phenomena such as inflammation, tumor angiogenesis, and epithelial-mesenchymal transition. BACH proteins are also regulated by proteins, miRNAs, LncRNAs, labile iron, and positive and negative feedback. Additionally, we summarize a list of regulators targeting these proteins. Our review provides a reference for future studies on targeted drugs in digestive diseases.

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Genome-Scale CRISPR Knockout Screening Identifies BACH1 as a Key Regulator of Aflatoxin B1-Induced Oxidative Damage

Cited by 12 publications

References 34 publications

Massively Parallel CRISPR-Cas9 Knockout Screening in Sheep Granulosa Cells for FSH Response Genes

Massively Parallel CRISPR-Cas9 Knockout Screening in Sheep Granulosa Cells for FSH Response Genes

Transcription factor BACH1 in cancer: roles, mechanisms, and prospects for targeted therapy

Pathophysiological role of BACH transcription factors in digestive system diseases

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