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A plant immune protein enables broad antitumor response by rescuing microRNA deficiency in cancers

ABSTRACT: A plant immune protein enables broad antitumor response by rescuing microRNA deficiency in cancers

PROVIDER: PRJNA813858 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
	SRR18271700_1.fastq.gz	Fastqsanger.gz
	SRR18271700_2.fastq.gz	Fastqsanger.gz
	SRR18271701_1.fastq.gz	Fastqsanger.gz
	SRR18271701_2.fastq.gz	Fastqsanger.gz

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A plant immune protein enables broad antitumor response by rescuing microRNA deficiency in cancers [mRNA-seq]

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A plant immune protein enables broad antitumor response by rescuing microRNA deficiency in cancers [mRNA-seq]

Project description:Cancer cells are featured with uncontrollable activation of cell cycle and proliferation,and microRNA deficiency drives tumorigenesis. The RNA-dependent RNA polymerase (RDR) is essential for small RNA-mediated immune response in plants, but absent in vertebrates with adaptive immunity. Here we show that ectopic expression of plant RDR1 can generally inhibit the proliferation of different cancer cells. Interestingly, we find that abnormal AGO2-free microRNA isoforms with 1-nucleotide shortening at the 3’ end are widely accumulated in many tumors. RDR1 with nucleotidyltransferase activity can recognize and modify these problematic microRNAs with mononucleotides to restore their AGO2 loading efficiency, which eventually rescues microRNA deficiency and elevates microRNA expression to target cell cycle in cancer specifically. The wide antitumor effects of RDR1 can be visualized in multiple xenograft tumor models in vivo, which can be realized by adeno-associated virus-mediated delivery. Altogether, we develop a broad microRNA-mediated antitumor stratagem using the plant immune protein RDR1.

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A plant immune protein enables broad antitumor response by rescuing microRNA deficiency in cancers [miRNA-seq]

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A plant immune protein enables broad antitumor response by rescuing microRNA deficiency in cancers

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Loss of HLF enables metastasis via cell-collagen interaction in solid cancers

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Project description:Engineered macrophage-based therapies offer promising potential for cancer treatment but are limited by slow, uncontrolled drug release and the risk of macrophage reprogramming into tumor-promoting phenotypes. Here, we developed a thermally induced macrophage autolysis release system, the macrophage-microbe encapsulation bomb (MME-Bomb), which combines engineered macrophages loaded with indocyanine green (ICG)-encapsulated nanoparticles and antitumor attenuated Salmonella typhimurium strain. This system utilizes photothermally triggered pyroptosis to induce controlled macrophage rupture within the tumor microenvironment, releasing intracellular bacteria to stimulate prolonged antitumor immunity. By integrating light-responsive biomodulation, our approach enables site-specific activation of engineered cells, enhancing the rapid delivery of therapeutic agents and maximizing the synergy between macrophage-based and bacterial therapies. In preclinical cancer models, MME-Bomb significantly reduces the tumor burden and improves survival outcomes, both alone and in combination with checkpoint inhibitors. This innovative strategy offers a versatile and precise framework for advancing cancer immunotherapies.

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