MicroRNA Structural Diversity and Its Link to Malignancy in Early-Stage Lung Adenocarcinoma

What is it about?

In this research, we demonstrated that the structural diversity of microRNAs (miRNAs) is linked to the gene expression patterns that define the malignant traits of early-stage lung adenocarcinoma. The D-score, a measuring index of cellular miRNA structural diversity, clearly distinguished early-stage lung adenocarcinoma (LUAD) patients with low and high risks of recurrence. IGF2BP3, a protein expressing during fetal development and in several cancers, was identified as a regulator of miRNA structural organization. Control of 3’-isomiRs by IGF2BP3 appears to regulate the cellular networks that determine the malignant characteristics of early-stage LUAD. These results suggest that abnormal regulation of miRNA structural diversity is a key factor in creating a malignant gene expression profile in cancer cells.

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Photo by Robina Weermeijer on Unsplash

Photo by Robina Weermeijer on Unsplash

Why is it important?

While we know that abnormalities of miRNA play an important role in the development of human cancers, details like how their structural diversity is controlled and connected to biological processes are under debated. Our findings suggest that IGF2BP3 regulates the cellular component of 3’-longer isoforms of miRNAs (called 3’-long isomiRs), which might be a key system in establishing malignant gene expression by modulating how miRNAs can access their targets. Although the differences in target accessibility between mature miRNAs and 3’-long isomiRs are considered minor, the accumulation of these small changes across many targets could significantly impact the behavior of cancer cells. This regulatory system could be a convenient way to help maintain the malignant characteristics of cancer cells.

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