Overexpression of KIF18A promotes cell proliferation, inhibits apoptosis, and independently predicts unfavorable prognosis in lung adenocarcinoma

Abstract

Kinesin family member 18A (KIF18A), as a member of the kinesin superfamily, is significantly overexpressed and abnormally functions in various human cancers. But, its expression profiling in the lung adenocarcinoma (LUAD) remains unclear. In the present work, using the data derived from the Cancer Genome Atlas (TCGA), we assessed the expression pattern and prognostic value of KIF18A in LUAD. In addition, we analyzed the underlying mechanism of its gene dysregulation. Experimental and bioinformatic analysis results showed that KIF18A expression was dramatically increased in LUAD tissues compared with the normal counterparts. Moreover, the patients with high KIF18A expression had significantly poorer overall survival (OS) and recurrence‐free survival (RFS). Univariate and multivariate analyses indicated that increased KIF18A expression was independently associated with unfavorable OS and RFS. In addition, by analyzing deep sequencing data from TCGA‐LUAD, we found that KIF18A mutation was detected in 2.6% of LUAD cases, and increased KIF18A expression was associated with genetic amplification rather than DNA methylation. Moreover, gene co‐expression network analysis revealed that a total of 339 KIF18A co‐expressed genes were detected and enriched in several tumor‐related pathways, especially cell cycle. Knockdown of KIF18A significantly inhibited cell proliferation in vitro and in vivo. Furthermore, silencing KIF18A induced LUAD cells apoptosis and arrested the cell cycle in the G2/M phase. KIF18A promotes cell proliferation, inhibits apoptosis, and is a valuable prognostic predictor and potential therapeutic target for the patients with LUAD. © 2019 IUBMB Life, 2019

Kinesin KIF18A is a novel PUM-regulated target promoting mitotic progression and survival of a human male germ cell line

“…TGCTs are the most common solid tumours in young men, and their incidence is on the rise (Rosen et al, 2011). Our finding that KIF18A depletion inhibits proliferation of TCam-2 cells, is consistent with previous reports showing KIF18A-stimulated proliferation of other cancer cells in vitro and in vivo, such as clear cell renal carcinoma, breast cancer or lung adenocarcinoma (Chen et al, 2016;Zhang et al, 2010;Zhong et al, 2019). In addition, the effect of KIF18A depletion, associated with upregulation of apoptosis and cell cycle arrest represent features promoting cancer.…”

“…Since it was reported that KIF18A influences mouse germ cell proliferation (Czechanski et al, 2015;Luo et al, 2018;Zhong et al, 2019), we first investigated whether human KIF18A induces such an effect on TCam-2 cells, a cell line that originates from male germ cells. For that purpose, we performed an MTS proliferation assay upon KIF18A knockdown, starting at 24 h up to 120 h post transfection.…”

HMGB1 Promotes the Proliferation and Metastasis of Lung Cancer by Activating the Wnt/β-Catenin Pathway

“… 2 However, most patients relapse within 5 years, and treatment options are limited. 13 , 14 Accurate molecular characterization of abnormal gene expression involved in the development and progression of lung cancer is essential for identifying novel molecular targets of non-small cell lung cancer (NSCLC), which may improve future clinical outcomes. 15 …”

Development of Multiscale Transcriptional Regulatory Network in Esophageal Cancer Based on Integrated Analysis

“…Among the regulators that were not finally selected, there were also some well-known factors that had been declared in cancer. Silencing KIF18A induced apoptosis in lung adenocarcinoma cells and blocked the cell cycle at G2/M phase, while overexpression of KIF18A might promote cell proliferation and inhibit apoptosis [35]. Moreover, Kim et al suggested that CYP4A11 expression was a potential poor prognostic factor of renal cell carcinoma [36].…”