Pan-cancer analysis of microRNA expression profiles highlights microRNAs enriched in normal body cells as effective suppressors of multiple tumor types

MicroRNAs (miRNAs) are frequently deregulated in various types of cancer. While antisense oligonucleotides are used to block oncomiRs, delivery of tumour-suppressive miRNAs holds great potential as a potent anticancer strategy. Here, we aim to determine, and functionally analyse, miRNAs that are lowly expressed in various types of tumour but abundantly expressed in multiple normal tissues. By compiling all publicly available miRNA profiling data from The Cancer Genome Atlas (TCGA) Pan-Cancer Project, we reveal a small set of tumour-suppressing miRNAs (which we designate as 'normomiRs') that are highly expressed in ۱۴ types of normal tissues but poorly expressed in corresponding tumour tissues. Interestingly, muscle-enriched miRNAs (e.g. miR-۱۳۳a/b and miR-۲۰۶) and miRNAs from DLK۱-DIO۳ locus (e.g. miR-۳۸۱ and miR-۴۱۱) constitute a large fraction of the normomiRs. Moreover, we define that the CCCGU motif is absent in the oncomiRs' seed sequences but present in a fraction of tumour-suppressive miRNAs. Finally, the gain of function of candidate normomiRs across several cancer cell types indicates that miR-۲۰۶ and miR-۳۸۱ exert the most potent inhibition on multiple cancer types in vitro. Overall, our results reveal a pan-cancer set of tumoursuppressing miRNAs and highlight the potential of miRNA-replacement therapies for targeting multiple types of tumour.

کلیدواژه ها:

tumorigenesis ، cancer cell ، miRNA ، cell viability ، proliferation