Few efficacious treatment options are available for patients with small cell lung carcinoma (SCLC), indicating the need to develop novel therapeutic approaches. In this study, we explored kinesin family member 11 (KIF11), a potential therapeutic target in SCLC. An analysis of publicly available data suggested that KIF11 mRNA expression levels are significantly higher in SCLC tissues than in normal lung tissues. When KIF11 was targeted by RNA interference or a small-molecule inhibitor (SB743921) in two SCLC cell lines, Lu-135 and NCI-H69, cell cycle progression was arrested at the G2/M phase with complete growth suppression. Further work suggested that the two cell lines were more significantly affected when both KIF11 and BCL2L1, an anti-apoptotic BCL2 family member, were inhibited. This dual inhibition resulted in markedly decreased cell viability. These findings collectively indicate that SCLC cells are critically dependent on KIF11 activity for survival and/or proliferation, as well as that KIF11 inhibition could be a new strategy for SCLC treatment.

EGFR-mutant lung adenocarcinoma (LUAD) mostly depends on EGFR for survival and consequently responds well to EGFR inhibitors. However, resistance to the drugs develops almost universally during treatment. We previously demonstrated that EGFR-mutant LUAD cell lines, HCC827 and H1975, have subpopulations of cells, which we termed HCC827 GR2 and H1975 WR7 cells, that can thrive independently of EGFR signaling. These EGFR-independent EGFR-mutant cancer cells are difficult to treat because they lack sensitivity to EGFR inhibitors. Therefore, the development of novel strategies to target EGFR-independent EGFR-mutant LUAD is particularly important. We found that high expression of kinesin family member 11 (KIF11) correlated with poor survival in patients with LUAD. We also observed that KIF11 silencing caused cell cycle arrest at G2/M in HCC827 GR2 and H1975 WR7 cells. Furthermore, dual silencing of KIF11 plus BCL2L1, an anti-apoptotic BCL2 family member, in these two EGFR-independent sublines resulted in marked apoptosis levels. Dual inhibition of KIF11 plus BCL2L1 also induced apoptosis in HCC827 and H1975 parental cells and a KRAS-mutant LUAD cell line, H441. These findings collectively suggest that dual inhibition of KIF11 plus BCL2L1 may be a new approach for the treatment of LUAD.

UNASSIGNED: Adrenocortical carcinoma (ACC) is a rare endocrine neoplasia with poor prognosis. Emerging evidence suggests that kinesin family member 11 (KIF11) protein is overexpressed in several tumors and associated with the onset and progression of certain types of cancer; however, its biological functions and mechanisms in ACC progression have not been studied yet. Therefore, this study evaluated the clinical significance and therapeutic potential of the KIF11 protein in ACC.
UNASSIGNED: The Cancer Genome Atlas (TCGA) database (n=79) and Genotype Tissue Expression (GTEx) database (n=128) were utilized to explore the expression of KIF11 in ACC and normal adrenal tissues. The TCGA datasets were then data mined and statistically analyzed. R survival analysis and univariate and multivariate Cox regression analyses were used to evaluate the effect of KIF11 expression on the survival rates, and a nomogram was used to predict its impact on prognosis. The clinical data from 30 ACC patients\' from Xiangya Hospital were also analyzed. The effects of KIF11 on the proliferation and invasion of ACC NCI-H295R were further validated in vitro.
UNASSIGNED: Analytical data from the TCGA and GTEx databases showed that KIF11 expression was upregulated in ACC tissues and associated with T (primary tumor), and M (metastasis) and stages of tumor progression. Increased KIF11 expression was significantly associated with shorter overall survival, disease-specific survival, and progression-free intervals. Clinical data from Xiangya Hospital illustrated that increased KIF11 had a significantly positive correlation with shorter overall survival, T and pathological stages, and tumor recurrence risk. Monastrol, a specific inhibitor of KIF11, was further confirmed to significantly inhibit the proliferation and invasion of ACC NCI-H295R cell in vitro. The nomogram demonstrated KIF11 was an excellent predictive biomarker in patients with ACC.
UNASSIGNED: The findings demonstrate that KIF11 could be a predictor of poor prognosis and thus possibly serve as a novel therapeutic target for ACC.

UNASSIGNED: Cutaneous squamous cell carcinoma (cSCC), a common skin malignancy, often occurs at exposed sites, and patients\' appearance after surgical resection can be affected. This study sought to screen the key genes of cSCC via a bioinformatics analysis and explore the clinical significance and possible potential mechanisms of these genes in cSCC.
UNASSIGNED: We screened differentially expressed genes (DEGs) between cSCC and normal skin tissues from the Gene Expression Omnibus database, performed functional enrichment and protein interaction network analyses, and used Cytoscape software to identify the key genes. The expression of the genes was proved by immunohistochemistry.
UNASSIGNED: A total of 164 DEGs were screened, and the functional enrichment analysis showed that the DEGs were significantly enriched in deoxyribonucleic acid replication and the cell-cycle pathway. By constructing a protein-to-protein interaction network, kinesin family member 11 (KIF11), aurora kinase A (AURKA), minichromosome maintenance complex component 2 (MCM2), minichromosome maintenance 10 replication initiation factor (MCM10), and denticleless E3 ubiquitin protein ligase homolog (DTL) were identified as 5 key genes with the highest connectivity. The expression of KIF11, AURKA, and MCM2 were investigated by immunohistochemistry. Compared to the normal skin tissues, the positive rates of the KIF11 and MCM2 proteins in the cSCC tissues were 70.0% and 90.0%, respectively, and the difference was statistically significant (P<0.05). The positive rates of AURKA protein expression in the cSCC and normal skin tissues were 13.9% and 0%, respectively, but the difference was not statistically significant. There was no correlation between the above-mentioned 3 key genes.
UNASSIGNED: KIF11 and MCM2 were highly expressed in cSCC, and may be involved in tumorigenesis, and represent novel targets for the clinical diagnosis and treatment of cSCC.