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

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.

Zhong Y ，Jiang L ，Lin H ，Li X ，Long X ，Zhou Y ，Li B ，Li Z ... -  《-》

High kinesin family member 18A expression correlates with poor prognosis in primary lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most prevalent pathological subtype of lung cancer. Kinesin family member 18A (KIF18A) plays an important role in tumorigenesis. Its roles in breast cancer, colorectal cancer, and other tumors have been demonstrated; however, studies of KIF18A in LUAD are limited. This study aimed to determine the role of KIF18A in LUAD progression and prognostic prediction. KIF18A expression was examined in LUAD cells and tissues by immunohistochemistry and Western blotting. Cell proliferation assay was performed to study the role of KIF18A in LUAD cells. Correlations between KIF18A expression and clinicopathological features were analyzed. The role of KIF18A in LUAD prognosis was evaluated using data from The Cancer Genome Atlas (TCGA). KIF18A expression was increased in tumor cells and tissues. Downregulation of KIF18A expression resulted in the suppression of cancer cell proliferation in in vitro assays, and was particularly related to poor tumor differentiation, big tumor size, lymph node metastasis, and more advanced tumor stage. In the TCGA dataset, high KIF18A messenger RNA expression was associated with poor disease-free and overall survival in patients with LUAD. In addition, multivariate analysis indicated that KIF18A is an independent prognostic factor of disease-free and overall survival in LUAD. Collectively, our results demonstrate that KIFl8A is highly expressed in LUAD. KIFl8A plays an important role in LUAD cell proliferation, but is a poor prognostic factor.

Li X ，Liu M ，Zhang Z ，Zhang L ，Liang X ，Sun L ，Zhong D ... -  《-》

Actin-like protein 8 promotes cell proliferation, colony-formation, proangiogenesis, migration and invasion in lung adenocarcinoma cells.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-associated mortality worldwide of which lung adenocarcinoma (LUAD) is the most common. The identification of oncogenes and effective drug targets is the key to individualized LUAD treatment. Actin-like protein 8 (ACTL8), a member of the cancer/testis antigen family, is associated with tumor growth and patient prognosis in various types of cancer. However, whether ACTL8 is involved in the development of LUAD remains unknown. The aim of the present study was to demonstrate the role of ACTL8 in human LUAD cells. The expression of ACTL8 in LUAD tissues and cell lines was assessed using immunohistochemistry and western blotting. Additionally, plasmids expressing ACTL8-specific short hairpin RNAs were used to generate lentiviruses which were subsequently used to infect A549 and NCI-H1975 human LUAD cells. Cell proliferation, migration, invasion and apoptosis, as well as cell cycle progression and the expression of protein markers of epithelial to mesenchymal transition were investigated. A549 cell tumor growth in nude mice was also examined. The results showed that ACTL8 was highly expressed in A549 and NCI-H1975 LUAD cell lines. Additionally, ACTL8-knockdown inhibited proliferation, colony formation, cell cycle progression, migration and invasion, and increased apoptosis in both cell lines. Furthermore, in vivo experiments in nude mice revealed that ACTL8-knockdown inhibited A549 cell tumor growth. These results suggest that ACTL8 serves an oncogenic role in human LUAD cells, and that ACTL8 may represent a potential therapeutic target for LUAD. Our results suggest that ACTL8 serves an oncogenic role in human LUAD cells, and that ACTL8 may represent a potential therapeutic target for LUAD.

Ma S ，Wang X ，Zhang Z ，Liu D ... -  《-》

USF1-induced overexpression of long noncoding RNA WDFY3-AS2 promotes lung adenocarcinoma progression via targeting miR-491-5p/ZNF703 axis.

Ren P ，Hong X ，Chang L ，Xing L ，Zhang H ... -  《-》

Genome‑wide investigation of the clinical significance and prospective molecular mechanisms of kinesin family member genes in patients with lung adenocarcinoma.

Zhang L ，Zhu G ，Wang X ，Liao X ，Huang R ，Huang C ，Huang P ，Zhang J ，Wang P ... -  《-》