Burgos-Aceves, M. A. | bioRxiv Science

bioRxiv2026

Tumor Suppression across the Human miRNome Associates with Guanine-Rich Precursor Terminal Loops

MicroRNAs (miRNAs) play essential regulatory roles in controlling cell growth, proliferation, and differentiation in cancer. While functional studies have identified numerous oncogenic (oncomiRs) and tumor suppressor (TS) miRNAs, the structural features that differentiate these groups remain poorly understood. Here, we performed a comprehensive sequence analysis of 955 human pre-miRNA terminal loops (TLs), focusing on enrichment of single guanine (G) and GG dinucleotides. A quantitative G enrichment score was used to define 42 G-rich TL miRNAs and 17 G-free TL miRNAs as controls. Functional roles of these miRNAs were curated from 757 publications. The results show that G-rich TL miRNAs consistently display higher TS/oncomiR ratios than G-free TL miRNAs across most cancer types, with a significant enrichment observed in lung cancer (p = 0.023). Focusing on miR-139, a TS miRNA with a G-rich TL, integrative analysis of publicly available transcriptomic and proteomic data revealed its consistent downregulation across all stages of lung adenocarcinoma (LUAD), accompanied by reciprocal overexpression of its validated oncogenic target, CCNB1. These findings highlight the biological relevance of G-rich TL structures in miRNA-mediated tumor suppression in lung cancer, suggesting their consideration in future therapeutic strategies aimed at restoring vulnerable TS miRNAs.

molecular biology↗

bioRxiv2019

Guanine content of microRNAs is associated with their tumor suppressive and oncogenic roles in lung and breast cancers

BackgroundmicroRNAs (miRNAs, miRs) are small noncoding RNAs that negatively regulate gene expression at the post-transcriptional level and fine-tune gene functions. A global repression of miRNAs expression in different types of human tumors, after exposure to cigarette-smoke, or to the hormone estrogen, have been shown to be associated with guanine (G) enrichment in the terminal loops (TLs) of their precursors. Methodswe integrated the G content of miRNA mature forms and precursor miRNA TLs with their described function in the literature, using the PubMed database. Gene Ontology term analysis was used to describe the pathways in which the G-enriched miRNA targets are involved. Resultswe show here an association between the relative G enrichment of precursor miRNAs TLs and their tendency to act as tumor suppressor miRs in human lung and breast cancers. Another association was observed between the high G content of the miRNAs 5-mature forms and their tendency to act as oncomiRs. Conclusionsthe results support previous findings showing that the G sequence content is an important feature determining miRNA expression and function, and open the way for future cancer investigations in this direction.

cancer biology↗