8-methylguanosine and Neoplasms

N

Topics: Guanosine; Humans; MicroRNAs; Neoplasms; RNA, Messenger

Intrahepatic cholangiocarcinoma (ICC) exhibits very low response rate to immune checkpoint inhibitors (ICIs) and the underlying mechanism is largely unknown. We investigate the tumour immune microenvironment (TIME) of ICCs and the underlying regulatory mechanisms with the aim of developing new target to inhibit tumour growth and improve anti-programmed cell death protein-1 (PD-1) efficacy.. Tumour tissues from patients with ICC together with hydrodynamic ICC mouse models were employed to identify the key cell population in TIME of ICCs. Functional analysis and mechanism studies were performed using cell culture, conditional knockout mouse model and hydrodynamic transfection ICC model. The efficacy of single or combined therapy with anti-PD-1 antibody, gene knockout and chemical inhibitor were evaluated in vivo.. Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are enriched in advanced ICCs and significantly correlated with N. Our data uncover novel mechanisms underlying chemokine regulation and TIME shaping at the layer of messenger RNA translation level and provide new insights for development of efficient cancer immunotherapeutic strategies.

Topics: Animals; Cell Line, Tumor; Guanosine; Humans; Mice; Myeloid-Derived Suppressor Cells; Neoplasms; RNA, Transfer; Tumor Microenvironment

N7-methylguanosine (m

Topics: Epigenesis, Genetic; Guanosine; Humans; Neoplasms

The emerging "epitranscriptomics" field is providing insights into the biological and pathological roles of different RNA modifications. The RNA methyltransferase METTL1 catalyzes N7-methylguanosine (m

Topics: Carcinogenesis; Guanosine; Humans; Methylation; Methyltransferases; Neoplasms; Oncogenes; RNA Processing, Post-Transcriptional; RNA, Messenger; RNA, Transfer; tRNA Methyltransferases