# KIF18B Is Essential for Lung Adenocarcinoma Progression Through the E2F Transcriptional Network

## TL;DR

This study identifies KIF18B as a key driver of lung adenocarcinoma progression through its role in the E2F transcriptional network.

## Contribution

The novel contribution is the discovery that KIF18B promotes LUAD progression via the E2F transcriptional network.

## Key findings

- KIF18B is significantly upregulated in LUAD and associated with poor patient survival.
- KIF18B knockdown suppresses LUAD cell proliferation, migration, and tumor growth.
- KIF18B regulates E2F target genes, and E2F overexpression rescues inhibited proliferation.

## Abstract

Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality worldwide, highlighting the urgent need to identify novel prognostic biomarkers and therapeutic targets. Kinesin Family Member 18B (KIF18B) is implicated in mitosis, yet its precise role in LUAD pathogenesis remains poorly defined. This study investigates the oncogenic and therapeutic role of KIF18B in LUAD. Integrated analysis of The Cancer Genome Atlas Program (TCGA) and Gene Expression Omnibus (GEO) datasets revealed that KIF18B is significantly upregulated in LUAD tissues, with its elevated expression strongly associated with an advanced pathological stage, high grade, and poor patient survival. Single-cell sequencing data analysis further indicated that KIF18B expression in LUAD is closely linked to key malignant processes, including cell cycle progression, proliferation, migration, and epithelial–mesenchymal transition (EMT). Functional experiments demonstrated that KIF18B knockdown markedly suppressed LUAD cell proliferation, migration, and invasion in vitro and inhibited tumor growth in vivo. Mechanistically, transcriptomic and pathway analyses revealed that KIF18B depletion downregulates Early 2 Factor (E2F) target genes. Luciferase reporter assays confirmed diminished E2F reporter activity as well as E2F2 promoter activity upon KIF18B silencing, while overexpression of E2F1, E2F2, or E2F3 rescued the inhibited proliferative phenotypes induced by KIF18B loss. Collectively, our findings establish KIF18B as an essential driver of LUAD progression that acts through the E2F transcriptional network, nominating it as a promising diagnostic and therapeutic target.