miR-139 is a Tumor Suppressor microRNA with a Guanine-rich Precursor Terminal Loop

Area of Science:

• Molecular Biology
• Genetics
• Oncology

Background:

• MicroRNAs (miRNAs) are crucial gene regulators involved in cancer development.
• While oncogenic and tumor suppressor miRNAs are known, their structural differences are unclear.
• Guanine (G) enrichment in precursor miRNA (pre-miRNA) terminal loops (TLs) is investigated for its association with tumor-suppressive activity.

Purpose of the Study:

• To investigate if G enrichment in pre-miRNA TL regions correlates with tumor-suppressive function in lung cancer.
• To analyze structural features distinguishing tumor suppressor (TS) miRNAs from oncogenic (oncomiRs) miRNAs.

Main Methods:

• Analyzed 955 human pre-miRNA TL sequences for G enrichment.
• Identified G-rich TL miRNAs using a G-enrichment score.
• Assessed miRNA expression and target regulation in lung adenocarcinoma (LUAD) using transcriptomic and proteomic data.

Main Results:

• G-rich TL miRNAs showed a higher ratio of TS to oncomiRs compared to G-free controls.
• TS miRNA enrichment in G-rich TLs was significantly higher in lung cancer than in the pan-cancer background (p = 0.027).
• miR-139, a TS miRNA with a G-rich TL, was downregulated in LUAD, with its target CCNB1 upregulated.

Conclusions:

• G-rich TL architecture is associated with TS miRNA function, particularly in lung cancer.
• TL G content may impact miRNA processing, stability, and activity.
• miR-139 and its target CCNB1 in LUAD exemplify the functional relevance of TL sequence composition in tumor suppression.