CC chemokine receptor-9 (CCR9) is highly expressed in non-small cell lung cancer (NSCLC) tissues and cell lines. However, the biological functions and the signals elicited by the interaction between CCR9 and its natural ligand CCL25 in NSCLC are unknown. Here, we selectively depleted CCR9 and inhibited CCR9-CCL25 interaction in NSCLC cells using small recombinant lentivirus-mediated miRNA, and investigated the tumorigenic effects in vitro and in vivo. Compromised CCR9-CCL25 interaction promoted apoptosis in NSCLC cells by activating phosphoinositide 3-kinase (PI3K)/Akt in vitro. In addition, we showed that CCR9-CCL25 interaction mediated the activation of the PI3K/Akt pathway in NSCLC cells, resulting in the up-regulation of anti-apoptotic proteins, as well as the down-regulation of apoptotic proteins in a PI3K-/Akt-dependent manner. These CCR9-CCL25-mediated effects were abrogated in the presence of a PI3K inhibitor (wortmannin 10 nM) or by inhibiting the CCR9-CCL25 interaction through CCR9 silencing, which also suggested that the biological function of CCR9-CCL25 was mainly regulated by PI3K. In vivo studies also demonstrated a significantly lower tumor burden in mice receiving CCR9-silence cells than those in mice receiving control cells. Together, these data suggested that CCR9-CCL25 interaction induced tumorigenesis of NSCLC cells and that this induction might be accomplished through the activation of the PI3K/Akt pathway. These findings may lead to a better understanding of the biological effects of CCR9-CCL25 interaction and provide clues for identifying novel therapeutic and preventive molecular markers for NSCLC.

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

CD59, belonging to membrane complement regulatory proteins (mCRPs), inhibits the cytolytic activity of complement and is overexpressed in many types of solid cancers. The aim of the present study was to detect the expression of CD59 in non-small cell lung cancer (NSCLC) and to investigate the relationship between decreased CD59 expression and tumorigenesis of NSCLC by transfecting recombinant retrovirus encoding shRNA targeting human CD59 into the human NSCLC cell line NCI-H157. CD59 expression in NSCLC was detected by immunocytochemistry (IHC). In the human NSCLC cell line NCI-H157, CD59 mRNA and protein expression suppressed with lentivirus-mediated RNAi was confirmed by using RT-PCR and western blotting, respectively. The proliferation and apoptosis of NCI-H157 cells was measured by using MTT assay and FACS. The resistance to complement cracking ability was detected by LDH assay. Caspase-3 expression in cells was assessed by IHC. Bcl-2 and Fas protein was determined by western blotting both in vitro and in vivo. CD59 is overexpressed in human NLCLC cancer. In NCI-H157 cells, lentivirus-mediated RNAi significantly reduced both CD59 mRNA and protein expression, which resulted in suppressing cell proliferation and increasing cell apoptosis. When incubated with fresh normal human serum (8%, v/v) for 1 h at 37˚C, the cell viability was decreased and cell apoptosis was increased in siCD59-infected NCI-H157 cells compared to siCD59-C-infected cells. Reduced CD59 expression led to increased expression of caspase-3 and Fas and decreased expression of Bcl-2. Furthermore, the nude mouse tumor graft weight was significantly decreased and survival rate was significantly increased in the siCD59 group. CD59 is overexpressed in human NLCLC. CD59 silencing in NSCLC cancer cells via retrovirus-mediated RNAi can enhance complement-mediated cell apoptosis, inhibiting the growth of NSCLC. CD59 may serve as a potential target for gene therapy in NSCLC.