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

ABSTRACT: 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.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE198145 | GEO | 2022/03/08

REPOSITORIES: GEO

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

2022-03-08 | GSE198146 | GEO

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Deep sequencing of small RNAs

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