# MiR-31 suppresses lung adenocarcinoma cell proliferation through CDK1 and E2F2-mediated cell cycle arrest

## TL;DR

MiR-31 helps stop lung cancer cell growth by targeting CDK1 and E2F2, offering a new way to treat lung adenocarcinoma.

## Contribution

MiR-31 is newly identified as a key regulator of CDK1/E2F2 in lung adenocarcinoma proliferation.

## Key findings

- CDK1 and E2F2 are significantly upregulated in lung adenocarcinoma tissues.
- Pharmacological inhibition of CDK1 reverses proliferative phenotypes in LUAD cells.
- MiR-31 is elevated in LUAD and regulates CDK1/E2F2, suggesting a therapeutic target.

## Abstract

MicroRNAs (miRNAs) exert pivotal regulatory functions in cancer initiation, progression, and metastasis by regulating cell proliferation-cycle related genes. However, tumor-associated miRNAs in lung adenocarcinoma (LUAD) remains incompletely characterized.

By interrogating TCGA mRNA-Seq datasets, we identified 1672 differentially expressed genes (DEGs) implicated in proliferation-cycle regulation in LUAD. A significant overrepresentation of transmembrane signal receptors, kinases, and TFs was observed among the DEGs, with primary enrichment in signaling pathways such as chemokine/cytokine, Wnt, EGF, Cadherin, and p53 cascades. Remarkably, CDK1 and E2F2 were characterized as key proliferation-cycle regulatory genes, demonstrating > fivefold transcriptional up-regulation in LUAD specimens compared to normal lung tissues (p < 0.001). Mechanistically, pharmacological CDK1 inhibition using fostamatinib or alsterpaullone reversed aberrant proliferative phenotypes in LUAD cells, demonstrating therapeutic reversibility in vitro. Concurrently, DEmiRNA and target analysis identified miR-31 as a critical regulator of CDK1/E2F2, showing elevated expression in LUAD.

Collectively, our study establishes miR-31 as a novel biomarker for LUAD proliferative potential and implicates the miR-31/CDK1-E2F2 network as a promising target for disrupting LUAD progression. These findings establish a miRNA-centric precision therapeutic paradigm for effectively suppressing oncogenic proliferation in LUAD.

The online version contains supplementary material available at 10.1007/s12672-025-04362-6.