CRISPR-mediated MECOM depletion retards tumor growth by reducing cancer stem cell properties in lung squamous cell carcinoma

Ma, Yuanyuan; Kang, Bin; Li, Shaolei; Xie, Guoyun; Bi, Jiwang; Li, Fuqiang; An, Guo; Liu, Bing; Li, Jing; Shen, Yue; Xu, Xun; Yang, Huanming; Yang, Yue; Gu, Ying; Wu, Nan

doi:10.1016/j.ymthe.2022.06.011

Cited by 10 publications

(2 citation statements)

References 51 publications

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“…High levels of MECOM expression are associated with a poor prognosis clinically. Consistently, enhanced expression of MECOM in LUSC cell lines was observed to promote the properties of cancer stem cells (CSCs), while knockout of it inhibits CSC phenotype (Ma et al, 2022).…”

Section: Crispr Screen For Gene Regulating Tumor Growthmentioning

confidence: 78%

Application of CRISPR screen in mechanistic studies of tumor development, tumor drug resistance, and tumor immunotherapy

Sun

Shi

2023

Front. Cell Dev. Biol.

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Tumor is one of the biggest threats to human health. Though tumor therapy has been dramatically advanced by the progress of technology and research in recent decades, it is still far from expectations. Thus, it is of great significance to explore the mechanisms of tumor growth, metastasis, and resistance. Screen based on Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR-associated protein (Cas) 9 gene editing technology are powerful tools for exploring the abovementioned facets. This review summarizes the recent screen performed in cancer cells and immune cells in the tumor microenvironment. The screens in cancer cells mainly focus on exploring the mechanisms underlying cancer cells’ growth, metastasis, and how cancer cells escape from the FDA approved drugs or immunotherapy. And the studies in tumor-associated immune cells are primarily aimed at identifying signaling pathways that can enhance the anti-tumor function of cytotoxic T lymphocytes (CTLs), CAR-T cells, and macrophages. Moreover, we discuss the limitations, merits of the CRISPR screen, and further its future application in tumor studies. Importantly, recent advances in high throughput tumor related CRISPR screen have deeply contributed to new concepts and mechanisms underlying tumor development, tumor drug resistance, and tumor immune therapy, all of which will eventually potentiate the clinical therapy for tumor patients.

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Section: Crispr Screen For Gene Regulating Tumor Growthmentioning

confidence: 78%

Application of CRISPR screen in mechanistic studies of tumor development, tumor drug resistance, and tumor immunotherapy

Sun

Shi

2023

Front. Cell Dev. Biol.

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“…After reviewing the existing literature, we found that the cancerpromoting or cancer-inhibiting function of some of the 27 DRGs in oncology has been reported. For example, MECOM (MDS1 and EVI1 complex locus), was reported to be engaged in modulating the cancer-stem-cell (CSC) properties in lung squamous carcinoma (56). Replication protein A3 (RPA3) inhibited protective autophagy and promoted cisplatin resistance in lung adenocarcinoma (57).…”

Section: Discussionmentioning

confidence: 99%

Risk stratification based on DNA damage-repair-related signature reflects the microenvironmental feature, metabolic status and therapeutic response of breast cancer

Chen

et al. 2023

Front. Immunol.

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DNA damage-repair machinery participates in maintaining genomic integrity and affects tumorigenesis. Molecular signatures based on DNA damage-repair-related genes (DRGs) capable of comprehensively indicating the prognosis, tumor immunometabolic profile and therapeutic responsiveness of breast cancer (BRCA) patients are still lacking. Integrating public datasets and bioinformatics algorithms, we developed a robust prognostic signature based on 27 DRGs. Multiple patient cohorts identified significant differences in various types of survival between high- and low-risk patients stratified by the signature. The signature correlated well with clinicopathological factors and could serve as an independent prognostic indicator for BRCA patients. Furthermore, low-risk tumors were characterized by more infiltrated CD8+ T cells, follicular helper T cells, M1 macrophages, activated NK cells and resting dendritic cells, and fewer M0 and M2 macrophages. The favorable immune infiltration patterns of low-risk tumors were also accompanied by specific metabolic profiles, decreased DNA replication, and enhanced antitumor immunity. Low-risk patients may respond better to immunotherapy, and experience improved outcomes with conventional chemotherapy or targeted medicine. Real-world immunotherapy and chemotherapy cohorts verified the predictive results. Additionally, four small molecule compounds promising to target high-risk tumors were predicted. In vitro experiments confirmed the high expression of GNPNAT1 and MORF4L2 in BRCA tissues and their association with immune cells, and the knockdown of these two DRGs suppressed the proliferation of human BRCA cells. In summary, this DNA damage-repair-related signature performed well in predicting patient prognosis, immunometabolic profiles and therapeutic sensitivity, hopefully contributing to precision medicine and new target discovery of BRCA.

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Advancements in organs-on-chips technology for viral disease and anti-viral research

Li¹,

Bai²,

Wang³

et al. 2023

Organs-on-a-Chip

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CRISPR-mediated MECOM depletion retards tumor growth by reducing cancer stem cell properties in lung squamous cell carcinoma

Cited by 10 publications

References 51 publications

Application of CRISPR screen in mechanistic studies of tumor development, tumor drug resistance, and tumor immunotherapy

Application of CRISPR screen in mechanistic studies of tumor development, tumor drug resistance, and tumor immunotherapy

Risk stratification based on DNA damage-repair-related signature reflects the microenvironmental feature, metabolic status and therapeutic response of breast cancer

Advancements in organs-on-chips technology for viral disease and anti-viral research

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